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Review

The Extracellular MicroRNAs on Inflammation: A Literature Review of Rodent Studies

by
Seri Lee
1,2,
Jade Heejae Ko
1 and
Seung-Nam Kim
1,*
1
College of Korean Medicine, Dongguk University, Goyang 10326, Korea
2
Graduate School, Dongguk University, Seoul 04620, Korea
*
Author to whom correspondence should be addressed.
Biomedicines 2022, 10(7), 1601; https://doi.org/10.3390/biomedicines10071601
Submission received: 14 June 2022 / Revised: 3 July 2022 / Accepted: 3 July 2022 / Published: 5 July 2022
(This article belongs to the Special Issue Extracellular microRNAs in Inflammatory Diseases)
Browse Figures
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Abstract

:
Inflammation is an indispensable biological process stimulated by infection and injuries. Inflammatory mechanisms related to extracellular vesicles (EVs), which are small membrane structures carrying various molecules, were summarized in this review. Emerging evidence from animal studies has highlighted the role of EVs in modulating inflammatory responses, by transporting various molecules involved in host defense. In this review, we have discussed the role of EV miRNAs in inflammation. Rodent studies associated with extracellular miRNAs in inflammatory diseases, published from 2012 to 2022, were explored from PUBMED, EMBASE, and MEDLINE. A total of 95 studies were reviewed. In summary, EV-associated miRNAs play a key role in various diseases, including organ injury, immune dysfunction, neurological disease, metabolic syndrome, vesicular disease, arthritis, cancer, and other inflammatory diseases. Diverse EV-associated miRNAs regulate inflammasome activation and pro- and anti-inflammatory cytokine levels by targeting genes.

Graphical Abstract

1. Introduction

The inflammatory response is a rapid and complex physiological process that involves defense mechanisms acting against infections and injuries [1,2]. Inflammation is often regarded as a failure of homeostasis between the host and immune cells. Dysregulation of the inflammatory response underlie various pathological conditions, including chronic inflammation [3], autoimmunity [4], neurodegenerative diseases [5], and cancer [6]. Previous discoveries in inflammatory processes have highlighted the physiological and cellular basis of inflammation under experimental conditions using bacterial lipopolysaccharide (LPS), peptidoglycan, and viral double-stranded RNA [7]. Intracellular signals sent to immune cell nuclei are followed by initial inflammatory cues, which stimulate various transcriptional changes [8]. In addition to the discovery of molecular mechanisms of regulation and initiation of inflammatory responses, a new perspective on inflammatory processes was revealed in recent decades, with the emerging interest in the discovery of mammalian microRNAs (miRNAs) and extracellular vesicles (EVs) [9,10].
EVs are small vesicles (30–10,000 nm in diameter) that can be categorized into the following three types according to their size and biogenesis: exosomes, microvesicles, and apoptotic bodies [11]. EVs are evident in almost all living cells and have been gaining attention as a novel mediator of communication between cells and numerous biological processes and regenerative properties [12,13]. Evs carry various molecules, such as proteins, mRNA [14], long non-coding RNA, circular RNAs, RNA, and miRNAs [10]. miRNAs are endogenous non-coding RNA molecules that use exosomes as carriers to achieve intercellular communication and regulation of protein biosynthesis, while being protected from degradation in the harsh extracellular environment [15]. Extracellular miRNAs have numerous functions in inflammatory processes [16,17], cell migration [18], apoptosis [19], and proliferation [20]. From the perspective of inflammatory responses, various extracellular miRNAs have recently been reported to be expressed in immune cells, affecting the magnitude of their responses [21]. Moreover, the structural stability of extracellular miRNAs has been widely recognized; extracellular miRNAs are now considered potential noninvasive biomarkers for inflammatory disease monitoring and prognosis [22].
This report presents an overview of the recent studies on extracellular miRNAs, with a focus on their role in inflammatory diseases in animals.

2. Study Methods

2.1. Literature Search

All relevant studies were initially searched on EMBASE, MEDLINE and PUBMED database using the following search keywords: “extracellular vesicles”, “exosome”, “inflammatory diseases”, and “microRNA”. We included rodent studies published from November 2012 to April 2022 and overlapping studies were excluded. Eventually, we identified 320 potentially relevant literatures for further eligibility assessments.

2.2. Study Selection

Three authors (S.L., J.H.K. and S.-N.K.) independently assessed the 320 literatures and a total of 208 studies were excluded based on the following exclusion criteria: (1) review article (n = 100); (2) full text not available (n = 1); (3) not English (n = 1), (4) virus or infection-induced experiment model (n = 14), (5) not a rodent study (n = 92). Title and abstract screening were performed and six studies with no specific microRNA target (n = 12) and five studies with no mention of microRNA mechanism were excluded. As shown in Figure 1, this study ultimately included a total of 95 articles for further analyses.

3. Main Text

3.1. Organ Injuries

Among the 95 articles, 35 articles were related to organ-injury-associated miRNAs in exosomes. The uncontrolled inflammatory response is one of the major factors among various causes of organ injuries. The miRNAs are known to target mRNAs and modulate the level of protein expression encoded by these mRNAs. We attempted to determine how miRNAs in exosomes influence organ injury-related diseases, including myocardial infarction, liver failure, ulcerative colitis, and acute lung injury (Table 1).

3.1.1. Liver Injury

In alcoholic and inflammatory liver diseases, serum/plasma miR-122 and miR-155 increased during drug-induced liver injury, and these miRNAs were present in the protein-rich fraction [23]. In a mouse model with autoimmune hepatitis (AIH) induced by hepatic injection of S100 protein, miR-223 in the exosomes derived from bone marrow mesenchymal stem cells (BMSCs) protected the liver from injury and inhibited NLRP3 activation that causes hepatic damage and liver dysfunction [24]. In hepatic fibrogenesis or fibrosis in a carbon tetrachloride-or thioacetic acid-induced liver injury mouse model, EVs of normal mice suppressed hepatocyte death and circulating pro-inflammatory cytokine levels. miR-34c, -151, -483, -532, and -687, which are highly expressed in EVs, have therapeutic effects in injured hepatocytes [25]. In acute liver failure induced in mice by LPS and D-GalN, miR-17 in AMSC-derived exosomes suppressed NLRP3 inflammasome activation by targeting TXNIP [26]. In a high-fat high-cholesterol diet-fed-induced NAFLD rat model, more exosomes were released, contained more miR-192, and the levels of M1-specific cytokines, such as iNOS, IL-6, and TNF-α, increased. miR-192 in exosomes from hepatocytes activated pro-inflammatory macrophages via Rictor/Akt/FoxO1 signaling [27]. In another experimental AIH mouse model, miR-223 carried in MSC exosomes attenuated liver injury and inflammatory responses [28]. In an endotoxemia and chemical liver injury induced by LPS, miR-455exosomes from hUC-MSCs attenuated macrophage infiltration and cured liver damage via PI3K signaling [29].

3.1.2. Lung Injury

In an acute lung injury (ALI) mouse model established by cecal ligation puncture (CLP), miR-125 in exosomes derived from endothelial cells promoted VEGF expression, inflammatory response, improved pathological changes, restrained lung water content, protein content in bronchoalveolar lavage fluid, and cell apoptosis by targeting TOP2A [30]. In an LPS-induced ALI rat model, miR-384 in exosomes derived from BMSC alleviated pathological changes in lung, pulmonary vascular permeability, and attenuated the inflammatory response by targeting Beclin-1 [31]. In a sepsis-induced lung injury mouse model and an LPS-induced AEC damage model, ADSCs exosomes promoted autophagy activation through the delivery of circ-Fryl and the regulation of the miR-490/SIRT3 pathway [32]. In a mouse model of CLP-induced septic lung injury, miR-16 in exosomes developed from ADSCs relieved lung injury and promoted macrophage polarization by suppressing TLR4 [33]. In another study on an LPS-induced ALI mouse model, miR-377 in exosomes from hucMSCs suppressed bronchoalveolar lavage, inflammatory factors, and ameliorated lung injury by targeting RPTOR [34]. In a hyperoxia-induced ALI model established using LPS or K. pneumoniae, microvesicles containing miR-223/142 targeted lung macrophages and suppressed inflammatory lung responses by blocking N1rp3 and Asc [35]. In another LPS-induced ALI rat model, miR-22 in exosomes derived from UCB-MSCs suppressed pathological changes, apoptosis, NF-κB expression, and oxidative stress response by reducing FZD6 levels [36].

3.1.3. Heart Injury

miR-133-MSC transplantation improved cardiac function, and miR-133-overexpressing MSCs repressed cardiac expression of snail-1 and reduced inflammation and fibrosis in the infarcted heart in a rat myocardial infarction model [37]. βARKct EVs altered pro- and anti-inflammatory cytokine levels and prevented heart failure in a myocardial infarction or catecholamine toxicity mouse model. The miRNA profiling revealed that miR-7004 and mi7-7b were upregulated in βARKct present in EVs [38]. In a rat model of hypoxia-induced H9c2 myocardial cell injury, miR-126-enhanced ADSC-derived exosomes decreased the myocardial injury area of infarction, cardiac fibrosis, and inflammatory cytokine expression [39]. In a doxorubicin/trastuzumab-induced cardiac toxicity rat model, cardiac progenitor cell-derived exosomes were highly enriched in miR-146a that prevented myocardial fibrosis, CD68+ inflammatory cell infiltration, inducible nitric oxide synthase expression, and left ventricular dysfunction [40]. In an acute myocardial infarction rat model produced by surgical ligation of the left anterior descending coronary artery, exosomes from miR-146a-ADSCs promoted myocardial cell apoptosis, inflammatory response, and fibrosis, and attenuated myocardial infarction by downregulating EGR1 [41]. Using the same rat model, cardioprotection was observed by exosomes from miR-25-MSCs, and exosomes attenuated myocardial infarction by targeting EZH2 and pro-apoptotic proteins [42]. In a sepsis-induced mouse with myocardial infarction, miR-24 in exosomes derived from M2 macrophages had cardioprotective effects and alleviated myocardial injury by suppressing Tnfsf10 [43]. miR-223 targeted SEMA3A and STAT3, and this miRNA in mice exosomes, had cardioprotective effects in CLP-induced sepsis [44]. In a mouse model of myocardial infarction caused by coronary artery ligation, exosomes overexpressing miR-129 showed enhanced cardiac function and production of inflammatory cytokines, and inhibited apoptosis and fibrosis by targeting HMGB1 [45]. In angiotensin II-induced hypertrophy in rat cardiomyocytes, hypertrophic cardiomyocyte-derived exosomes regulated macrophage activation and induced phosphorylation of ERK, JNK, and p38 through the miR-155-mediated MAPK pathway [46].

3.1.4. Bowel Disease

In a dextran sulfate sodium (DSS)-induced colitis mouse model, miR-378 carried by hucMSC exosomes attenuated colitis by regulating macrophage pyroptosis and inhibiting NLRP3 inflammasome activation [47]. Moreover, miR-590 carried by M2 macrophage exosomes suppressed inflammatory signals and promoted epithelial repair via the LATS1/YAP/β-catenin signaling axis [48]. Another study on the same model showed that miR-21a in M1 exosomes attenuated DSS-induced enteritis by decreasing the expression of E-cadherin and subsequent activation of ILC2s via KLRG1/GATA-3 [49]. In a rat small bowel transplantation model of allograft rejection, miR-200b in exosomes derived from heme oxygen-1 (HO-1)-modified BMSCs alleviated inflammatory injury of intestinal epithelial cells (IECs) by targeting Hmgb3 [50].

3.1.5. Kidney Injury

In the ischemia/reperfusion-injured mouse kidney, miR-23a-enriched exosomes from hypoxic tubular epithelial cells promoted tubulointerstitial inflammation in mice by inhibiting A20; hence, miR-23a inhibition suppressed renal tubulointerstitial inflammation [51]. In a lethal renal ischemia/reperfusion injury rat model, miR-146a, in exosomes derived from USC, inhibited injury via IRAKI and inhibited the activation of NF-κB signaling [52]. A mouse model that was administered a high-fat diet and streptozotocin injection showed that inhibiting Rab27a attenuated inflammation through the miR-26a/CHAC1/NF-κB pathway in renal proximal tubular epithelial cells [53]. In a kidney injury mouse model induced by CLP, miR-21 expression in exosomes extracted from the serum of mice with limb remote ischemic preconditioning in remote organs attenuated sepsis-induced renal injury and regulated the PDCD4/NF-κB and PTEN/AKT pathways [54].

3.1.6. Other Organs

In a taurocholate-induced acute pancreatitis rat model, pro-inflammatory miR-155 was increased in plasma exosomes, and miR-122 and miR-21 were decreased compared to that in plasma control exosomes. The levels of miRNAs in pancreatitis-associated ascitic fluid exosomes were similar to those in plasma control exosomes. Plasma exosomes had higher pro-inflammatory activity in macrophages [55]. In a rat model of urethral stricture generated with TGFβ1 injection, miR-146a in exosomes derived from TNF-α-treated MSCs inhibited fibroblast activation and suppressed the inflammatory response, TRAF6, IRAK1, and NF-κB signaling [56]. In an acute uterine injury mouse model induced by LPS, miR-223 enriched BMSC-Exos degraded NLRP3 via interaction with endothelial progenitor cells and suppressed LPS-induced cell pyroptosis [57].

3.2. Immune Dysfunction

Ten articles that we explored were related to the immune dysfunction of miRNAs in exosomes. Immune dysfunction is a disorder of the immune system that includes sepsis and asthma. Recent studies have investigated the roles of miRNAs in immune dysfunction and the associated diseases. We have now organized each miRNA that was introduced as the target of different immune dysfunction studies (Table 2).
For a Rab27KO mouse model that displays a chronic, low-grade inflammatory condition, exosomes carrying miR-155 can rescue LPS responsiveness, and the reduction in miR-155 targeting SHIP1 and IRAK-M is involved in this rescue [58]. In an intestinal lavage of a septic mouse model, pro-inflammatory cytokines TNF-α and IL-17A were suppressed by septic-EV injection, and pro-inflammatory cytokines were targeted by multiple miRNAs upregulated by sepsis-induced exosomes. IEC-derived luminal EVs carry miRNAs that can alleviate pro-inflammatory responses [59]. In a CLP mouse model with severe sepsis, miR-146a, miR-9, and miR-155 functioned as pro-inflammatory messengers. Choroid plexus-derived EVs into CSF transferred pro-inflammatory messages to recipient brain cells, and blockage of EV secretion inhibited brain inflammation [60]. Using mouse chimeras with Rab27KO EV-deficient T cells, miR-20a, miR-25, and miR-155, which are carried in T-cell EV-modulated key mRNA in B cells, promote proliferation, survival, and transfer of EV-miRNA-controlled germinal center reaction and antibody production [61]. In a CLP rat model of sepsis, miR-1 increased in exosomes, and it inhibited proliferation, and promoted apoptosis and cytoskeleton contraction via SERP1 [62]. A mouse model of asthma induced by ovalbumin and miR-370 carried by M2 macrophage-derived exosomes alleviated asthma progression by inhibiting the FGF1 and MAPK/STAT1 signaling pathways [63]. In a mouse model of colitis and systemic inflammation, exosomes transferring let-7d from Treg cells to Th1 cells contributed to the inhibition and suppression of systemic disease [64]. In another ovalbumin-induced asthma mouse model, miR-188 in exosomes derived from hBM-MSCs suppressed the proliferation of BSMCs and lung injury through the JARID2/Wnt/β-catenin axis [65]. In CLP-induced sepsis, miR-146a in exosomes derived from MSCs with IL-1b promoted macrophage polarization to the M2 phenotype, reduced inflammation, and increased the survival of mice [66]. Using an IL-10 KO mouse model of systemic inflammation, endothelial progenitor cell exosomes improved endothelial cell proliferation and tube formation, and inhibited apoptosis. With IL-10 deficiency, impaired function was observed. Modulation of enriched miR-375 rescued IL-10KO-EPC-Exo dysfunction [67].

3.3. Neurological Disease

Only 13 articles included in this study were related to neurological diseases of miRNA in exosomes. Neurological diseases are associated with nervous system disorders. Here, we have discussed the roles or attenuation of miRNAs in exosomes in neurological diseases (Table 3).
In a mouse with middle cerebral artery occlusion used for cerebral infarction model, exosome-miR-542 derived from MSCs suppressed cerebral injury and inflammation by inhibiting TLR4 [68]. In a stress-induced depression mouse model, levels of BDNF, TrkB, and synaptotagmin 1 were decreased in the hippocampus, PFC, and serum exosomes. The miRNA profiling revealed that differentially expressed miRNAs were possibly involved in the pathogenesis of depression through the MAPK, Wnt, and mTOR pathways [69]. In an amyotrophic lateral sclerosis mouse model, miR-467f and miR-466q associated with MSC-derived s-EV reduced neuroinflammation. Furthermore, miR-467f and miR-466q reduce the activation of p38 MAPK signaling by inhibiting Map3k8 and Mk2 [70]. Using a repetitive traumatic brain injury mouse model, a study showed that miR-124 in exosomes improved neurologic outcomes and inhibited neuroinflammation by targeting PDE4B, thus suppressing mTOR signaling [71]. A study on a mouse model of endotoxemia induced by LPS that stimulated neuroinflammation revealed that the inflammatory cytokine mRNA, miR-155, and systemic inflammatory cytokine production increased. The serum-derived exosomes elevated inflammation-related miRNAs, such as miR-21, miR-125a, miR-146a, and miR-155. These miRNAs were engaged in modulating TLR signaling [72]. Using a chronic mild stress mouse model of depression, NK cell-derived exosomes carrying miR-207 alleviated symptoms such as depression and decreased pro-inflammatory cytokines, targeted TLR4, and hence an inhibited NF-κB signaling in astrocytes [73]. In a rat model of spinal cord injury, miR-544 in exosomes derived from BMSC attenuated histological deficits and neuronal loss, and inhibited inflammation induced by spinal cord injury [74]. Another study used a rat model of spinal cord injury and revealed that exosomes improved neuroprotective effects through the miR-219a-2/YY1 axis [75]. In a mouse model of spared nerve injury, miR-21 antagomir in the dorsal root ganglia reduced pro-inflammatory macrophage infiltration, and miR-21 deletion in sensory neurons reduced neuropathic hypersensitivity [76]. For an ischemic brain injury rat model established by middle cerebral artery occlusion, miR-181c in the cortical neuron released exosomes that inhibited neuroinflammation by suppressing CXCL1 [77]. In a mouse model with KA-induced epileptic seizures, circHivep2 exosomes prevented microglial cell activation and inflammatory factors through the miR-181a/SOCS2 mechanism [78]. In a mouse model of Alzheimer’s disease induced by LPS, miR-146a was enriched in EVs under inflammatory conditions, and EVs can induce inflammation and LPS tolerance [79]. Using the APP/PS1 mouse model of Alzheimer’s disease, miR-22 in exosomes from ADMSC enhanced neurological function, inhibited PC12 apoptosis, and decreased inflammatory factors by inhibiting proptosis [80].

3.4. Metabolic Syndrome

Only seven of the ninety-five articles explored were related to metabolic syndromes involving miRNAs of exosomes. Metabolic syndrome increases the risk of heart disease, diabetes, and other health problems. Here, we determined how miRNAs in exosomes play a role in metabolic syndrome (Table 4).
In a streptozotocin (STZ)-induced diabetic rat model, miR-21 exosomes from MSCs promoted ulceration repair, ischemic hindlimb blood perfusion, ischemic repair, and angiogenesis [81]. Using a non-diabetic NOD mouse model of type 1 diabetes, the increase in serum EV miR-21 preceded hyperglycemia and circulating EV miR-21 could be a biomarker of developing type 1 diabetes [82]. In a mouse model, miR-17 containing hucMSCs-derived exosomes alleviated oxidative injury by inhibiting STAT1 [83]. In a mouse model of dietary obesity induced by STC nutrition and a high-fat diet (HFD), miR-34a of adipocyte-secreted exosomal vesicles led to obesity-induced metabolic dysfunction and M2 macrophage proliferation by inhibiting KLF4 [84]. Using the plasma exosomes from a glycogen storage disease type 1a mouse model, differentially expressed miRNAs were correlated with various pathologic liver states and circulating miRNAs could be a biomarker of glycogen storage disease type 1a [85]. In the case of a type 2 diabetic mouse, miR-29 promoted inflammation and diabetes via TRAF3 [86]. In an obese mouse model established by feeding a HFD, miR-690 in exosomes from M2-polarized bone marrow-derived macrophages improved insulin sensitivity via NADK [87].

3.5. Vesicular Disease

Among the 95 articles, only 8 articles were associated with miRNAs exosomes in vesicular disease. Vesicular disease is a kind of blood vessel disorder, which can occur in the location of different types of artery and veins. We organized the relations between miRNA exosomes and versicular diseases (Table 5).
In a mouse model of atherosclerotic diabetes, EPC-derived exosomes and its miRNAs ameliorated diabetic atherosclerotic plaques, endothelial dysfunction, and inflammatory factors [88]. In an atherosclerosis mouse model established by feeding a HFD, IRES-Il-10 mRNA carried in exosomes can be activated by miR-155 and alleviate local inflammation [89]. miR-512 enriched by MSC-derived exosomes had a protective effect on EC cells against oxidized low-density lipoprotein via targeting KEAP1 [90]. In the same HFD-induced atherosclerosis mouse model, hUCMSC-derived exosomes carrying miR-100 decreased the atherosclerotic plaque area and inflammation via FZD5/WNT/β-catenin pathway [91]. In a mouse model of hypoxic pulmonary hypertension, MSC-derived exosomes inhibited STAT3 and increased the miR-17 microRNA superfamily [92]. In another HFD-induced atherosclerosis mouse model, MSCs-exosomes suppressed the atherosclerotic plaque area and macrophage infiltration via let-7/HMGA2/NF-kB pathway [93]. In an atherosclerosis mouse model established by feeding a HFD, miR-146a derived from oxidized low-density lipoprotein treated THP-1 cells exosomes enhanced the atherosclerotic plaque area and led to atherosclerosis deterioration via targeting SOD2 [94]. In the rat myocardial ischemia-reperfusion injury model, miR-98 in exosomes from hypoxic BMSCs promoted cardiac function and suppressed the inflammation response by targeting TLR4, and thus activating the PI3K/Akt signaling pathway [95].

3.6. Arthritis

Six of the ninety-five articles studied were related to miRNA exosomes involved in arthritis. Arthritis is a disorder that commonly affects joints. This usually makes it difficult for them to be active. We examined how exosomal miRNAs influence arthritis (Table 6).
In a mouse model of mBSA-induced arthritis, the injection of anti-miR-132 attenuated inflammatory arthritis [96]. In a mouse model of osteoarthritis, miR-206 in exosomes from BMSC promoted proliferation and osteoblast differentiation by inhibiting ELF3 [97]. In another rat model of arthritis, miR-223 in exosomes from BMSCs regulated inflammasome activation by inhibiting NLRP3 [98]. Using an osteoarthritis rat model established by surgery, researchers found that miR-361 from hBMSC-derived exosomes alleviated chondrocyte damage by inhibiting DDX20; thus, the NF-κB signaling pathway was inactivated [99]. In a collagen-induced arthritis (CIA) mouse model, miR-146a in MSC-derived exosomes increased FOXP3, TGFβ, IL-10, and miR-155 levels that increased RORγt, IL-17, and IL-6 levels. Such modulations altered Treg cell levels and possibly improved the recovery of appropriate T-cell responses in RA [100]. In a CIA rat model, miR-192 in exosomes developed from BMSCs reduced the inflammatory response by targeting RAC2 [101].

3.7. Cancer

Only five of the ninety-five articles we studied were associated with roles of miRNA exosomes in cancer. Cancer is a type of disease with abnormally increased growth of cells that spreads easily, commonly leading to low survival rates. We discussed the relationships between the different types of cancer and miRNAs in exosomes and determined the underlying mechanism (Table 7).
In a mouse model, tumor growth was decreased by miR-155, whereas miR-205 increased tumor growth. miR-155 and miR-205 play important roles in tumor growth of breast cancer cells in mice [102]. In a breast tumor mouse model, miR-183 in exosomes derived from tumor cells decreased tumor growth and promoted pro-inflammatory cytokines by targeting PPP2CA [103]. In a tumor initiated by xenografts of lung tumor cells of mice, the injection of miR-101 suppressed lung tumor growth, macrophage tumor infiltration, and inflammation and inhibited CDK8 and Ki-67 expression [104]. In an intracranial mouse glioma model induced by injections of GL261 glioma cells, uptake of glioma cell-released EVs by microglia and monocytes/macrophages in the brain increased miR-21, decreased c-Myc mRNA, and increased the proliferation of mouse microglia [105]. In an azoxymethane/DSS-induced colitis-associated colorectal cancer model, miR-146a transfected into hucMSC-derived exosomes alleviated cancer progression by inhibition of SUMO1 [106].

3.8. Other Inflammatory Diseases

Eleven articles were discussed that dealt with other inflammatory diseases. We examined the mechanisms of action of miRNA exosomes in diverse diseases (Table 8).
In a ligature-induced periodontitis and diet-induced obesity mouse model, an miR-25 inhibitor suppressed local inflammation, and exosomes of miR-25 in saliva contributed to the advancement of diabetes-associated periodontitis [107]. Using a rat model of skull defects, a study found that exosomes from adipose-derived stem cells improved bone healing and regulated M1/M2 macrophage polarization via the miR-451a/MIF axis [108]. In a femoral defect model established by surgery, miR-181b in exosomes promoted osteointegration and suppressed the inflammatory response via the PRKCD/AKT axis [109]. In an acute graft-versus-host disease mouse model, miR-223 in exosomes derived from MSCs inhibited inflammatory cytokines and attenuated disease progression by suppressing donor T-cell migration [110]. A study using a tendon defect model showed that miR-144 enriched in exosomes from tendon-derived stem cells improved the injured tendons. The performance of biomechanical testing was enhanced by targeting ARID1A [111]. In a cisplatin-induced hearing loss mouse model, miRNAs such as miR-125a, miR-125b, and miR-127 were highly abundant in UCMSC exosomes that improved hearing loss through reduced cochlear hair cell loss [112]. In a dimethylbenzanthracene-induced oral potentially malignant disorder (OPMDs) hamster model, miR-185 in extracellular vesicles derived from MSCs alleviated the inflammatory response and suppressed the progression of OPMDs by targeting AKT [113]. In a mouse model of intervertebral disc degeneration, established using the puncture method and H2O2 exposure, platelet-rich plasma exosomes enriched with miR-141 suppressed IVD degeneration by activating the KEAP1/NRF2 pathway [114]. In preterm birth induced by lipopolysaccharides (LPS), miR-146a levels were elevated. miR-146a and miR-548e from amniotic fluid-derived MSCs showed anti-inflammatory effects on human trophoblasts [115]. In a periodontitis rat model induced by LPS, miR-17 in periodontal ligament stem cells was suppressed by inflammation and alleviated its target VEGFA [116]. In an IL-1β-induced intervertebral disc degeneration model, miR-142 in exosomes derived from BMSCs alleviated NPC injury by targeting MLK3, thus inhibiting MAPK signaling [117].

4. Conclusions

Experimental studies of EVs and miRNAs are newly emerging and are in demand. We focused on diverse EV-associated miRNAs that play crucial roles in various inflammatory diseases. In this review, we have discussed the association of miRNAs in EVs with inflammatory diseases in rodent models. EVs have been recognized as the cargo of various molecules transported from origin cells to recipient cells mostly in all organisms. EVs also play complex and important roles in the pathophysiology of several diseases. Moreover, diverse EV-associated miRNAs play crucial roles in various inflammatory diseases. Given the previously suggested functions of EVs and increasing interest in clinical implications of EVs in various diseases, this study focused on miRNA in EVs in inflammatory diseases to further analyze their involvement in inflammatory responses. However, the studies included in this review are insufficient for comprehensive knowledge about the mode of action of extracellular miRNAs in inflammation. In addition, the included studies mostly reported changes in miRNA expression in different disease models, yet there was limited evidence of how the loss or gain of each miRNA function work in disease conditions. Further functional studies on each miRNA in inflammatory disease are needed to confirm the use of extracellular miRNAs as potential biomarkers or as a therapeutic method in which they can be safely and efficiently delivered to the target region. Nevertheless, our understanding suggests an opportunity for further study of extracellular miRNAs as biomarkers and the early diagnosis of inflammatory diseases and disorders. Moreover, the use of EVs might further offer the possibility of gene therapeutic approaches for inflammation.

Author Contributions

Conceptualization, S.L.; investigation, S.L.; writing—original draft preparation, S.L. and J.H.K.; writing—review and editing, S.-N.K.; supervision, S.-N.K. All authors have read and agreed to the published version of the manuscript.

Funding

This work was supported by the National Research Foundation of Korea funded by the Korean government (MSIT) (NRF-2020R1C1C1004107) and from the Ministry of Health and Welfare through the Korea Health Industry Development Institute (KHIDI) (grant no. HF21C0018).

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Chen, L.; Deng, H.; Cui, H.; Fang, J.; Zuo, Z.; Deng, J.; Li, Y.; Wang, X.; Zhao, L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 2018, 9, 7204–7218. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. A current view on inflammation. Nat. Immunol. 2017, 18, 825. [CrossRef] [PubMed] [Green Version]
  3. Furman, D.; Campisi, J.; Verdin, E.; Carrera-Bastos, P.; Targ, S.; Franceschi, C.; Ferrucci, L.; Gilroy, D.W.; Fasano, A.; Miller, G.W.; et al. Chronic inflammation in the etiology of disease across the life span. Nat. Med. 2019, 25, 1822–1832. [Google Scholar] [CrossRef]
  4. Duan, L.; Rao, X.; Sigdel, K.R. Regulation of Inflammation in Autoimmune Disease. J. Immunol. Res. 2019, 2019, 1–2. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  5. Guzman-Martinez, L.; Maccioni, R.B.; Andrade, V.; Navarrete, L.P.; Pastor, M.G.; Ramos-Escobar, N. Neuroinflammation as a Common Feature of Neurodegenerative Disorders. Front. Pharmacol. 2019, 10, 1008. [Google Scholar] [CrossRef] [Green Version]
  6. Zhao, H.; Wu, L.; Yan, G.; Chen, Y.; Zhou, M.; Wu, Y.; Li, Y. Inflammation and tumor progression: Signaling pathways and targeted intervention. Signal Transduct. Target. Ther. 2021, 6, 1–46. [Google Scholar] [CrossRef]
  7. Mogensen, T.H. Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses. Clin. Microbiol. Rev. 2009, 22, 240–273. [Google Scholar] [CrossRef] [Green Version]
  8. Carpenter, S.; Fitzgerald, K.A. Transcription of Inflammatory Genes: Long Noncoding RNA and Beyond. J. Interf. Cytokine Res. 2015, 35, 79–88. [Google Scholar] [CrossRef] [Green Version]
  9. Yang, Q.; Diamond, M.P.; Al-Hendy, A. The emerging role of extracellular vesicle-derived miRNAs: Implication in cancer progression and stem cell related diseases. J. Clin. Epigenetics 2016, 2, 13. [Google Scholar]
  10. O’Brien, K.; Breyne, K.; Ughetto, S.; Laurent, L.C.; Breakefield, X.O. RNA delivery by extracellular vesicles in mammalian cells and its applications. Nat. Rev. Mol. Cell Biol. 2020, 21, 585–606. [Google Scholar] [CrossRef]
  11. Doyle, L.; Wang, M. Overview of Extracellular Vesicles, Their Origin, Composition, Purpose, and Methods for Exosome Isolation and Analysis. Cells 2019, 8, 727. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  12. Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J.J.; Lötvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat. Cell Biol. 2007, 9, 654–659. [Google Scholar] [CrossRef] [Green Version]
  13. Silvestro, S.; Chiricosta, L.; Gugliandolo, A.; Pizzicannella, J.; Diomede, F.; Bramanti, P.; Trubiani, O.; Mazzon, E. Extracellular Vesicles Derived from Human Gingival Mesenchymal Stem Cells: A Transcriptomic Analysis. Genes 2020, 11, 118. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  14. Surgucheva, I.; Sharov, V.S.; Surguchov, A. γ-Synuclein: Seeding of α-Synuclein Aggregation and Transmission between Cells. Biochemistry 2012, 51, 4743–4754. [Google Scholar] [CrossRef]
  15. Li, C.; Ni, Y.-Q.; Xu, H.; Xiang, Q.-Y.; Zhao, Y.; Zhan, J.-K.; He, J.-Y.; Li, S.; Liu, Y.-S. Roles and mechanisms of exosomal non-coding RNAs in human health and diseases. Signal Transduct. Target. Ther. 2021, 6, 1–31. [Google Scholar] [CrossRef]
  16. Alexander, M.; Hu, R.; Runtsch, M.C.; Kagele, D.A.; Mosbruger, T.L.; Tolmachova, T.; Seabra, M.; Round, J.L.; Ward, D.M.; O’Connell, R.M. Exosome-delivered microRNAs modulate the inflammatory response to endotoxin. Nat. Commun. 2015, 6, 7321. [Google Scholar] [CrossRef] [Green Version]
  17. Li, Y.; Tan, J.; Miao, Y.; Zhang, Q. MicroRNA in extracellular vesicles regulates inflammation through macrophages under hypoxia. Cell Death Discov. 2021, 7, 1–12. [Google Scholar] [CrossRef] [PubMed]
  18. Yao, J.; Wang, Z.; Cheng, Y.; Ma, C.; Zhong, Y.; Xiao, Y.; Gao, X.; Li, Z. Correction to: M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway. J. Transl. Med. 2021, 19, 1–14. [Google Scholar] [CrossRef] [PubMed]
  19. Taghavipour, M.; Sadoughi, F.; Mirzaei, H.; Yousefi, B.; Moazzami, B.; Chaichian, S.; Mansournia, M.A.; Asemi, Z. Apoptotic functions of microRNAs in pathogenesis, diagnosis, and treatment of endometriosis. Cell Biosci. 2020, 10, 1–9. [Google Scholar] [CrossRef]
  20. Xu, P.; Wu, Q.; Lu, D.; Yu, J.; Rao, Y.; Kou, Z.; Fang, G.; Liu, W.; Han, H. A systematic study of critical miRNAs on cells proliferation and apoptosis by the shortest path. BMC Bioinform. 2020, 21, 1–14. [Google Scholar] [CrossRef]
  21. Wu, C.-J.; Lu, L.-F. MicroRNA in Immune Regulation. Curr. Top. Microbiol. Immunol. 2017, 410, 249–267. [Google Scholar] [CrossRef] [PubMed]
  22. Zhou, B.; Xu, K.; Zheng, X.; Chen, T.; Wang, J.; Song, Y.; Shao, Y.; Zheng, S. Application of exosomes as liquid biopsy in clinical diagnosis. Signal Transduct. Target. Ther. 2020, 5, 1–14. [Google Scholar] [CrossRef] [PubMed]
  23. Bala, S.; Petrasek, J.; Mundkur, S.; Catalano, D.; Levin, I.; Ward, J.; Alao, H.; Kodys, K.; Szabo, G. Circulating microRNAs in exosomes indicate hepatocyte injury and inflammation in alcoholic, drug-induced, and inflammatory liver diseases. Hepatology 2012, 56, 1946–1957. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  24. Chen, L.; Lu, F.-B.; Chen, D.-Z.; Wu, J.-L.; Hu, E.-D.; Xu, L.-M.; Zheng, M.-H.; Li, H.; Huang, Y.; Jin, X.-Y.; et al. BMSCs-derived miR-223-containing exosomes contribute to liver protection in experimental autoimmune hepatitis. Mol. Immunol. 2018, 93, 38–46. [Google Scholar] [CrossRef] [PubMed]
  25. Chen, L.; Chen, R.; Kemper, S.; Cong, M.; You, H.; Brigstock, D.R. Therapeutic effects of serum extracellular vesicles in liver fibrosis. J. Extracell. Vesicles 2018, 7, 1461505. [Google Scholar] [CrossRef] [PubMed]
  26. Liu, Y.; Lou, G.; Li, A.; Zhang, T.; Qi, J.; Ye, D.; Zheng, M.; Chen, Z. AMSC-derived exosomes alleviate lipopolysaccharide/d-galactosamine-induced acute liver failure by miR-17-mediated reduction of TXNIP/NLRP3 inflammasome activation in macrophages. eBioMedicine 2018, 36, 140–150. [Google Scholar] [CrossRef] [Green Version]
  27. Liu, X.-L.; Pan, Q.; Cao, H.-X.; Xin, F.-Z.; Zhao, Z.-H.; Yang, R.-X.; Zeng, J.; Zhou, H.; Fan, J.-G. Lipotoxic Hepatocyte-Derived Exosomal MicroRNA 192-5p Activates Macrophages Through Rictor/Akt/Forkhead Box Transcription Factor O1 Signaling in Nonalcoholic Fatty Liver Disease. Hepatology 2020, 72, 454–469. [Google Scholar] [CrossRef]
  28. Lu, F.-B.; Chen, D.-Z.; Chen, L.; Hu, E.-D.; Wu, J.-L.; Li, H.; Gong, Y.-W.; Lin, Z.; Wang, X.-D.; Li, J.; et al. Attenuation of Experimental Autoimmune Hepatitis in Mice with Bone Mesenchymal Stem Cell-Derived Exosomes Carrying MicroRNA-223-3p. Mol. Cells 2019, 42, 906–918. [Google Scholar] [CrossRef]
  29. Shao, M.; Xu, Q.; Wu, Z.; Chen, Y.; Shu, Y.; Cao, X.; Chen, M.; Zhang, B.; Zhou, Y.; Yao, R.; et al. Exosomes derived from human umbilical cord mesenchymal stem cells ameliorate IL-6-induced acute liver injury through miR-455-3p. Stem Cell Res. Ther. 2020, 11, 1–13. [Google Scholar] [CrossRef]
  30. Jiang, L.; Ni, J.; Shen, G.; Xia, Z.; Zhang, L.; Xia, S.; Pan, S.; Qu, H.; Li, X. Upregulation of endothelial cell-derived exosomal microRNA-125b-5p protects from sepsis-induced acute lung injury by inhibiting topoisomerase II alpha. Agents Actions 2021, 70, 205–216. [Google Scholar] [CrossRef]
  31. Liu, X.; Gao, C.; Wang, Y.; Niu, L.; Jiang, S.; Pan, S. BMSC-Derived Exosomes Ameliorate LPS-Induced Acute Lung Injury by miR-384-5p-Controlled Alveolar Macrophage Autophagy. Oxidative Med. Cell. Longev. 2021, 2021, 1–23. [Google Scholar] [CrossRef] [PubMed]
  32. Shen, W.; Zhao, X.; Li, S. Exosomes Derived from ADSCs Attenuate Sepsis-Induced Lung Injury by Delivery of Circ-Fryl and Regulation of the miR-490-3p/SIRT3 Pathway. Inflammation 2021, 45, 331–342. [Google Scholar] [CrossRef] [PubMed]
  33. Tian, J.; Cui, X.; Sun, J.; Zhang, J. Exosomal microRNA-16-5p from adipose mesenchymal stem cells promotes TLR4-mediated M2 macrophage polarization in septic lung injury. Int. Immunopharmacol. 2021, 98, 107835. [Google Scholar] [CrossRef] [PubMed]
  34. Wei, X.; Yi, X.; Lv, H.; Sui, X.; Lu, P.; Li, L.; An, Y.; Yang, Y.; Yi, H.; Chen, G. MicroRNA-377-3p released by mesenchymal stem cell exosomes ameliorates lipopolysaccharide-induced acute lung injury by targeting RPTOR to induce autophagy. Cell Death Dis. 2020, 11, 1–14. [Google Scholar] [CrossRef]
  35. Zhang, D.; Lee, H.; Wang, X.; Groot, M.; Sharma, L.; Cruz, C.S.D.; Jin, Y. A potential role of microvesicle-containing miR-223/142 in lung inflammation. Thorax 2019, 74, 865–874. [Google Scholar] [CrossRef] [PubMed]
  36. Zheng, Y.; Liu, J.; Chen, P.; Lin, L.; Luo, Y.; Ma, X.; Lin, J.; Shen, Y.; Zhang, L. Exosomal miR-22-3p from human umbilical cord blood-derived mesenchymal stem cells protects against lipopolysaccharid-induced acute lung injury. Life Sci. 2021, 269, 119004. [Google Scholar] [CrossRef]
  37. Chen, Y.; Zhao, Y.; Chen, W.; Xie, L.; Zhao, Z.-A.; Yang, J.; Chen, Y.; Lei, W.; Shen, Z. MicroRNA-133 overexpression promotes the therapeutic efficacy of mesenchymal stem cells on acute myocardial infarction. Stem Cell Res. Ther. 2017, 8, 1–11. [Google Scholar] [CrossRef]
  38. Kwon, J.-S.; Schumacher, S.M.; Gao, E.; Chuprun, J.K.; Ibetti, J.; Roy, R.; Khan, M.; Kishore, R.; Koch, W.J. Characterization of βARKct engineered cellular extracellular vesicles and model specific cardioprotection. Am. J. Physiol. Circ. Physiol. 2021, 320, H1276–H1289. [Google Scholar] [CrossRef]
  39. Luo, Q.; Guo, D.; Liu, G.; Chen, G.; Hang, M.; Jin, M. Exosomes from MiR-126-Overexpressing Adscs Are Therapeutic in Relieving Acute Myocardial Ischaemic Injury. Cell. Physiol. Biochem. 2017, 44, 2105–2116. [Google Scholar] [CrossRef]
  40. Milano, G.; Biemmi, V.; Lazzarini, E.; Balbi, C.; Ciullo, A.; Bolis, S.; Ameri, P.; Di Silvestre, D.; Mauri, P.; Barile, L.; et al. Intravenous administration of cardiac progenitor cell-derived exosomes protects against doxorubicin/trastuzumab-induced cardiac toxicity. Cardiovasc. Res. 2020, 116, 383–392. [Google Scholar] [CrossRef]
  41. Pan, J.; Alimujiang, M.; Chen, Q.; Shi, H.; Luo, X. Exosomes derived from miR-146a-modified adipose-derived stem cells attenuate acute myocardial infarction–induced myocardial damage via downregulation of early growth response factor 1. J. Cell. Biochem. 2018, 120, 4433–4443. [Google Scholar] [CrossRef] [PubMed]
  42. Peng, Y.; Zhao, J.-L.; Peng, Z.-Y.; Xu, W.-F.; Yu, G.-L. Exosomal miR-25-3p from mesenchymal stem cells alleviates myocardial infarction by targeting pro-apoptotic proteins and EZH2. Cell Death Dis. 2020, 11, 1–15. [Google Scholar] [CrossRef] [PubMed]
  43. Sun, X.; Liu, Y.; Wang, J.; Zhang, M.; Wang, M. Cardioprotection of M2 macrophages-derived exosomal microRNA-24-3p/Tnfsf10 axis against myocardial injury after sepsis. Mol. Immunol. 2021, 141, 309–317. [Google Scholar] [CrossRef] [PubMed]
  44. Wang, X.; Gu, H.; Qin, D.; Yang, L.; Huang, W.; Essandoh, K.; Wang, Y.; Caldwell, C.C.; Peng, T.; Zingarelli, B.; et al. Exosomal miR-223 Contributes to Mesenchymal Stem Cell-Elicited Cardioprotection in Polymicrobial Sepsis. Sci. Rep. 2015, 5, 13721. [Google Scholar] [CrossRef] [Green Version]
  45. Wang, S.; Dong, J.; Li, L.; Wu, R.; Xu, L.; Ren, Y.; Hu, X. Exosomes derived from miR-129-5p modified bone marrow mesenchymal stem cells represses ventricular remolding of mice with myocardial infarction. J. Tissue Eng. Regen. Med. 2021, 16, 177–187. [Google Scholar] [CrossRef]
  46. Yu, H.; Qin, L.; Peng, Y.; Bai, W.; Wang, Z. Exosomes Derived from Hypertrophic Cardiomyocytes Induce Inflammation in Macrophages via miR-155 Mediated MAPK Pathway. Front. Immunol. 2021, 11, 606045. [Google Scholar] [CrossRef]
  47. Cai, X.; Zhang, Z.-Y.; Yuan, J.-T.; Ocansey, D.K.W.; Tu, Q.; Zhang, X.; Qian, H.; Xu, W.-R.; Qiu, W.; Mao, F. hucMSC-derived exosomes attenuate colitis by regulating macrophage pyroptosis via the miR-378a-5p/NLRP3 axis. Stem Cell Res. Ther. 2021, 12, 1–16. [Google Scholar] [CrossRef]
  48. Deng, F.; Yan, J.; Lu, J.; Luo, M.; Xia, P.; Liu, S.; Wang, X.; Zhi, F.; Liu, D. M2 Macrophage-Derived Exosomal miR-590-3p Attenuates DSS-Induced Mucosal Damage and Promotes Epithelial Repair via the LATS1/YAP/β-Catenin Signalling Axis. J. Crohns Colitis 2020, 15, 665–677. [Google Scholar] [CrossRef]
  49. Lu, J.; Liu, D.; Tan, Y.; Deng, F.; Li, R. M1 Macrophage exosomes MiR-21a-5p aggravates inflammatory bowel disease through decreasing E-cadherin and subsequent ILC2 activation. J. Cell. Mol. Med. 2021, 25, 3041–3050. [Google Scholar] [CrossRef]
  50. Sun, D.; Cao, H.; Yang, L.; Lin, L.; Hou, B.; Zheng, W.; Shen, Z.; Song, H. MiR-200b in heme oxygenase-1-modified bone marrow mesenchymal stem cell-derived exosomes alleviates inflammatory injury of intestinal epithelial cells by targeting high mobility group box 3. Cell Death Dis. 2020, 11, 1–18. [Google Scholar] [CrossRef]
  51. Li, Z.-L.; Lv, L.-L.; Tang, T.-T.; Wang, B.; Feng, Y.; Zhou, L.-T.; Cao, J.-Y.; Tang, R.-N.; Wu, M.; Liu, H.; et al. HIF-1α inducing exosomal microRNA-23a expression mediates the cross-talk between tubular epithelial cells and macrophages in tubulointerstitial inflammation. Kidney Int. 2018, 95, 388–404. [Google Scholar] [CrossRef] [PubMed]
  52. Li, X.; Liao, J.; Su, X.; Li, W.; Bi, Z.; Wang, J.; Su, Q.; Huang, H.; Wei, Y.; Gao, Y.; et al. Human urine-derived stem cells protect against renal ischemia/reperfusion injury in a rat model via exosomal miR-146a-5p which targets IRAK1. Theranostics 2020, 10, 9561–9578. [Google Scholar] [CrossRef] [PubMed]
  53. Li, S.; Jia, Y.; Xue, M.; Hu, F.; Zheng, Z.; Zhang, S.; Ren, S.; Yang, Y.; Si, Z.; Wang, L.; et al. Inhibiting Rab27a in renal tubular epithelial cells attenuates the inflammation of diabetic kidney disease through the miR-26a-5p/CHAC1/NF-kB pathway. Life Sci. 2020, 261, 118347. [Google Scholar] [CrossRef] [PubMed]
  54. Pan, T.; Jia, P.; Chen, N.; Fang, Y.; Liang, Y.; Guo, M.; Ding, X. Delayed Remote Ischemic Preconditioning ConfersRenoprotection against Septic Acute Kidney Injury via Exosomal miR-21. Theranostics 2019, 9, 405–423. [Google Scholar] [CrossRef]
  55. Jiménez-Alesanco, A.; Marcuello, M.; Pastor-Jiménez, M.; López-Puerto, L.; Bonjoch, L.; Gironella, M.; Carrascal, M.; Abian, J.; De-Madaria, E.; Closa, D. Acute pancreatitis promotes the generation of two different exosome populations. Sci. Rep. 2019, 9, 1–13. [Google Scholar] [CrossRef] [Green Version]
  56. Liang, Y.; Wu, Y.; Li, X.; Chen, S.; Ye, X.; Xue, X.; Xu, N. TNF-α-induced exosomal miR-146a mediates mesenchymal stem cell-dependent suppression of urethral stricture. J. Cell. Physiol. 2019, 234, 23243–23255. [Google Scholar] [CrossRef]
  57. Liu, Y.; Zhang, S.; Xue, Z.; Zhou, X.; Tong, L.; Liao, J.; Pan, H.; Zhou, S. Bone mesenchymal stem cells-derived miR-223-3p-containing exosomes ameliorate lipopolysaccharide-induced acute uterine injury via interacting with endothelial progenitor cells. Bioengineered 2021, 12, 10654–10665. [Google Scholar] [CrossRef]
  58. Alexander, M.; Ramstead, A.G.; Bauer, K.M.; Lee, S.-H.; Runtsch, M.C.; Wallace, J.; Huffaker, T.B.; Larsen, D.K.; Tolmachova, T.; Seabra, M.C.; et al. Rab27-Dependent Exosome Production Inhibits Chronic Inflammation and Enables Acute Responses to Inflammatory Stimuli. J. Immunol. 2017, 199, 3559–3570. [Google Scholar] [CrossRef] [Green Version]
  59. Appiah, M.G.; Park, E.J.; Darkwah, S.; Kawamoto, E.; Akama, Y.; Gaowa, A.; Kalsan, M.; Ahmad, S.; Shimaoka, M. Intestinal Epithelium-Derived Luminally Released Extracellular Vesicles in Sepsis Exhibit the Ability to Suppress TNF-a and IL-17A Expression in Mucosal Inflammation. Int. J. Mol. Sci. 2020, 21, 8445. [Google Scholar] [CrossRef]
  60. Balusu, S.; Van Wonterghem, E.; De Rycke, R.; Raemdonck, K.; Stremersch, S.; Gevaert, K.; Brkic, M.; Demeestere, D.; Vanhooren, V.; Hendrix, A.; et al. Identification of a novel mechanism of blood–brain communication during peripheral inflammation via choroid plexus-derived extracellular vesicles. EMBO Mol. Med. 2016, 8, 1162–1183. [Google Scholar] [CrossRef]
  61. Fernández-Messina, L.; Galan, A.R.; De Yébenes, V.G.; Gutiérrez-Vázquez, C.; Tenreiro, S.; Seabra, M.; Ramiro, A.R.; Sánchez-Madrid, F. Transfer of extracellular vesicle-micro RNA controls germinal center reaction and antibody production. EMBO Rep. 2020, 21, e48925. [Google Scholar] [CrossRef] [PubMed]
  62. Gao, M.; Yu, T.; Liu, D.; Shi, Y.; Yang, P.; Zhang, J.; Wang, J.; Liu, Y.; Zhang, X. Sepsis plasma-derived exosomal miR-1-3p induces endothelial cell dysfunction by targeting SERP1. Clin. Sci. 2021, 135, 347–365. [Google Scholar] [CrossRef] [PubMed]
  63. Li, C.; Deng, C.; Zhou, T.; Hu, J.; Dai, B.; Yi, F.; Tian, N.; Jiang, L.; Dong, X.; Zhu, Q.; et al. MicroRNA-370 carried by M2 macrophage-derived exosomes alleviates asthma progression through inhibiting the FGF1/MAPK/STAT1 axis. Int. J. Biol. Sci. 2021, 17, 1795–1807. [Google Scholar] [CrossRef] [PubMed]
  64. Okoye, I.S.; Coomes, S.M.; Pelly, V.S.; Czieso, S.; Papayannopoulos, V.; Tolmachova, T.; Seabra, M.C.; Wilson, M.S. MicroRNA-Containing T-Regulatory-Cell-Derived Exosomes Suppress Pathogenic T Helper 1 Cells. Immunity 2014, 41, 89–103. [Google Scholar] [CrossRef] [Green Version]
  65. Shan, L.; Liu, S.; Zhang, Q.; Zhou, Q.; Shang, Y. Human bone marrow-mesenchymal stem cell-derived exosomal microRNA-188 reduces bronchial smooth muscle cell proliferation in asthma through suppressing the JARID2/Wnt/β-catenin axis. Cell Cycle 2022, 21, 352–367. [Google Scholar] [CrossRef]
  66. Song, Y.; Dou, H.; Li, X.; Zhao, X.; Li, Y.; Liu, D.; Ji, J.; Liu, F.; Ding, L.; Ni, Y.; et al. Exosomal miR-146a Contributes to the Enhanced Therapeutic Efficacy of Interleukin-1β-Primed Mesenchymal Stem Cells Against Sepsis. Stem Cells 2017, 35, 1208–1221. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  67. Yue, Y.; Garikipati, V.N.S.; Verma, S.K.; Goukassian, D.A.; Kishore, R. Interleukin-10 Deficiency Impairs Reparative Properties of Bone Marrow-Derived Endothelial Progenitor Cell Exosomes. Tissue Eng. Part A 2017, 23, 1241–1250. [Google Scholar] [CrossRef]
  68. Cai, G.; Cai, G.; Zhou, H.; Zhuang, Z.; Liu, K.; Pei, S.; Wang, Y.; Wang, H.; Wang, X.; Xu, S.; et al. Mesenchymal stem cell-derived exosome miR-542-3p suppresses inflammation and prevents cerebral infarction. Stem Cell Res. Ther. 2021, 12, 1–12. [Google Scholar] [CrossRef]
  69. Fang, K.; Xu, J.-X.; Chen, X.-X.; Gao, X.-R.; Huang, L.-L.; Du, A.-Q.; Jiang, C.; Ge, J.-F. Differential serum exosome microRNA profile in a stress-induced depression rat model. J. Affect. Disord. 2020, 274, 144–158. [Google Scholar] [CrossRef]
  70. Giunti, D.; Marini, C.; Parodi, B.; Usai, C.; Milanese, M.; Bonanno, G.; de Rosbo, N.K.; Uccelli, A. Role of miRNAs shuttled by mesenchymal stem cell-derived small extracellular vesicles in modulating neuroinflammation. Sci. Rep. 2021, 11, 1740. [Google Scholar] [CrossRef]
  71. Huang, S.; Ge, X.; Yu, J.; Han, Z.; Yin, Z.; Li, Y.; Chen, F.; Wang, H.; Zhang, J.; Lei, P. Increased miR-124-3p in microglial exosomes following traumatic brain injury inhibits neuronal inflammation and contributes to neurite outgrowth via their transfer into neurons. FASEB J. 2017, 32, 512–528. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  72. Li, J.J.; Wang, B.; Kodali, M.C.; Chen, C.; Kim, E.; Patters, B.J.; Lan, L.; Kumar, S.; Wang, X.; Yue, J.; et al. In vivo evidence for the contribution of peripheral circulating inflammatory exosomes to neuroinflammation. J. Neuroinflammation 2018, 15, 8. [Google Scholar] [CrossRef] [PubMed]
  73. Li, D.; Wang, Y.; Jin, X.; Hu, D.; Xia, C.; Xu, H.; Hu, J. NK cell-derived exosomes carry miR-207 and alleviate depression-like symptoms in mice. J. Neuroinflammation 2020, 17, 126. [Google Scholar] [CrossRef] [Green Version]
  74. Li, C.; Li, X.; Zhao, B.; Wang, C. Exosomes derived from miR-544-modified mesenchymal stem cells promote recovery after spinal cord injury. Arch. Physiol. Biochem. 2020, 126, 369–375. [Google Scholar] [CrossRef] [PubMed]
  75. Ma, K.; Xu, H.; Zhang, J.; Zhao, F.; Liang, H.; Sun, H.; Li, P.; Zhang, S.; Wang, R.; Chen, X. Insulin-like growth factor-1 enhances neuroprotective effects of neural stem cell exosomes after spinal cord injury via an miR-219a-2-3p/YY1 mechanism. Aging 2019, 11, 12278–12294. [Google Scholar] [CrossRef]
  76. Simeoli, R.; Montague, K.; Jones, H.R.; Castaldi, L.; Chambers, D.; Kelleher, J.H.; Vacca, V.; Pitcher, T.; Grist, J.; Al-Ahdal, H.; et al. Exosomal cargo including microRNA regulates sensory neuron to macrophage communication after nerve trauma. Nat. Commun. 2017, 8, 1778. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  77. Song, H.; Zhang, X.; Chen, R.; Miao, J.; Wang, L.; Cui, L.; Ji, H.; Liu, Y. Cortical Neuron-Derived Exosomal MicroRNA-181c-3p Inhibits Neuroinflammation by Downregulating CXCL1 in Astrocytes of a Rat Model with Ischemic Brain Injury. Neuroimmunomodulation 2019, 26, 217–233. [Google Scholar] [CrossRef]
  78. Xiaoying, G.; Guo, M.; Jie, L.; Yanmei, Z.; Ying, C.; Shengjie, S.; Haiyan, G.; Feixiang, S.; Sihua, Q.; Jiahang, S. CircHivep2 contributes to microglia activation and inflammation via miR-181a-5p/SOCS2 signalling in mice with kainic acid-induced epileptic seizures. J. Cell. Mol. Med. 2020, 24, 12980–12993. [Google Scholar] [CrossRef]
  79. Yang, J.; Malone, F.; Go, M.; Kou, J.; Lim, J.-E.; Caughey, R.C.; Fukuchi, K.-I. Lipopolysaccharide-Induced Exosomal miR-146a Is Involved in Altered Expression of Alzheimer’s Risk Genes Via Suppression of TLR4 Signaling. J. Mol. Neurosci. 2020, 71, 1245–1255. [Google Scholar] [CrossRef]
  80. Zhai, L.; Shen, H.; Sheng, Y.; Guan, Q. ADMSC Exo-MicroRNA-22 improve neurological function and neuroinflammation in mice with Alzheimer’s disease. J. Cell. Mol. Med. 2021, 25, 7513–7523. [Google Scholar] [CrossRef]
  81. Huang, C.; Luo, W.; Wang, Q.; Ye, Y.; Fan, J.; Lin, L.; Shi, C.; Wei, W.; Chen, H.; Wu, Y.; et al. Human mesenchymal stem cells promote ischemic repairment and angiogenesis of diabetic foot through exosome miRNA-21-5p. Stem Cell Res. 2021, 52, 102235. [Google Scholar] [CrossRef] [PubMed]
  82. Lakhter, A.J.; Pratt, R.E.; Moore, R.E.; Doucette, K.K.; Maier, B.F.; DiMeglio, L.A.; Sims, E.K. Beta cell extracellular vesicle miR-21-5p cargo is increased in response to inflammatory cytokines and serves as a biomarker of type 1 diabetes. Diabetologia 2018, 61, 1124–1134. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  83. Li, W.; Jin, L.-Y.; Cui, Y.-B.; Xie, N. Human umbilical cord mesenchymal stem cells-derived exosomal microRNA-17-3p ameliorates inflammatory reaction and antioxidant injury of mice with diabetic retinopathy via targeting STAT1. Int. Immunopharmacol. 2020, 90, 107010. [Google Scholar] [CrossRef] [PubMed]
  84. Pan, Y.; Hui, X.; Hoo, R.L.C.; Ye, D.; Chan, C.Y.C.; Feng, T.; Wang, Y.; Lam, K.S.L.; Xu, A. Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation. J. Clin. Investig. 2019, 129, 834–849. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  85. Resaz, R.; Cangelosi, D.; Morini, M.; Segalerba, D.; Mastracci, L.; Grillo, F.; Bosco, M.C.; Bottino, C.; Colombo, I.; Eva, A. Circulating exosomal microRNA as potential biomarkers of hepatic injury and inflammation inGlycogen storage disease type 1a. Dis. Models Mech. 2020, 13, dmm043364. [Google Scholar] [CrossRef]
  86. Sun, Y.; Zhou, Y.; Shi, Y.; Zhang, Y.; Liu, K.; Liang, R.; Sun, P.; Chang, X.; Tang, W.; Zhang, Y.; et al. Expression of miRNA-29 in Pancreatic β Cells Promotes Inflammation and Diabetes via TRAF3. Cell Rep. 2021, 34, 108576. [Google Scholar] [CrossRef]
  87. Ying, W.; Gao, H.; Dos Reis, F.C.G.; Bandyopadhyay, G.; Ofrecio, J.M.; Luo, Z.; Ji, Y.; Jin, Z.; Ly, C.; Olefsky, J.M. MiR-690, an exosomal-derived miRNA from M2-polarized macrophages, improves insulin sensitivity in obese mice. Cell Metab. 2021, 33, 781–790.e5. [Google Scholar] [CrossRef]
  88. Bai, S.; Yin, Q.; Dong, T.; Dai, F.; Qin, Y.; Ye, L.; Du, J.; Zhang, Q.; Chen, H.; Shen, B. Endothelial progenitor cell–derived exosomes ameliorate endothelial dysfunction in a mouse model of diabetes. Biomed. Pharmacother. 2020, 131, 110756. [Google Scholar] [CrossRef]
  89. Bu, T.; Li, Z.; Hou, Y.; Sun, W.; Zhang, R.; Zhao, L.; Wei, M.; Yang, G.; Yuan, L. Exosome-mediated delivery of inflammation-responsive Il-10 mRNA for controlled atherosclerosis treatment. Theranostics 2021, 11, 9988–10000. [Google Scholar] [CrossRef]
  90. Chen, S.; Zhou, H.; Zhang, B.; Hu, Q. Exosomal miR-512-3p derived from mesenchymal stem cells inhibits oxidized low-density lipoprotein-induced vascular endothelial cells dysfunction via regulating Keap1. J. Biochem. Mol. Toxicol. 2021, 35, e22767. [Google Scholar] [CrossRef]
  91. Gao, H.; Yu, Z.; Li, Y.; Wang, X. miR-100-5p in human umbilical cord mesenchymal stem cell-derived exosomes mediates eosinophilic inflammation to alleviate atherosclerosis via the FZD5/Wnt/β-catenin pathway. Acta Biochim. Biophys. Sin. 2021, 53, 1166–1176. [Google Scholar] [CrossRef] [PubMed]
  92. Lee, C.; Mitsialis, S.A.; Aslam, M.; Vitali, S.H.; Vergadi, E.; Konstantinou, G.; Sdrimas, K.; Fernandez-Gonzalez, A.; Kourembanas, S. Exosomes Mediate the Cytoprotective Action of Mesenchymal Stromal Cells on Hypoxia-Induced Pulmonary Hypertension. Circulation 2012, 126, 2601–2611. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  93. Li, J.; Xue, H.; Li, T.; Chu, X.; Xin, D.; Xiong, Y.; Qiu, W.; Gao, X.; Qian, M.; Xu, J.; et al. Exosomes derived from mesenchymal stem cells attenuate the progression of atherosclerosis in ApoE(-/-) mice via miR-let7 mediated infiltration and polarization of M2 macrophage. Biochem. Biophys. Res. Commun. 2019, 510, 565–572. [Google Scholar] [CrossRef] [PubMed]
  94. Zhang, Y.-G.; Song, Y.; Guo, X.-L.; Miao, R.-Y.; Fu, Y.-Q.; Miao, C.-F.; Zhang, C. Exosomes derived from oxLDL-stimulated macrophages induce neutrophil extracellular traps to drive atherosclerosis. Cell Cycle 2019, 18, 2672–2682. [Google Scholar] [CrossRef]
  95. Zhang, L.; Wei, Q.; Liu, X.; Zhang, T.; Wang, S.; Zhou, L.; Zou, L.; Fan, F.; Chi, H.; Sun, J.; et al. Exosomal microRNA-98-5p from hypoxic bone marrow mesenchymal stem cells inhibits myocardial ischemia–reperfusion injury by reducing TLR4 and activating the PI3K/Akt signaling pathway. Int. Immunopharmacol. 2021, 101, 107592. [Google Scholar] [CrossRef]
  96. Donate, P.B.; de Lima, K.A.; Peres, R.S.; Almeida, F.; Fukada, S.Y.; Silva, T.A.; Nascimento, D.C.; Cecilio, N.T.; Talbot, J.; Oliveira, R.D.; et al. Cigarette smoke induces miR-132 in Th17 cells that enhance osteoclastogenesis in inflammatory arthritis. Proc. Natl. Acad. Sci. USA 2020, 118, e2017120118. [Google Scholar] [CrossRef]
  97. Huang, Y.; Zhang, X.; Zhan, J.; Yan, Z.; Chen, D.; Xue, X.; Pan, X. Bone marrow mesenchymal stem cell–derived exosomal miR-206 promotes osteoblast proliferation and differentiation in osteoarthritis by reducing Elf3. J. Cell. Mol. Med. 2021, 25, 7734–7745. [Google Scholar] [CrossRef]
  98. Huang, Y.; Lu, D.; Ma, W.; Liu, J.; Ning, Q.; Tang, F.; Li, L. miR-223 in exosomes from bone marrow mesenchymal stem cells ameliorates rheumatoid arthritis via downregulation of NLRP3 expression in macrophages. Mol. Immunol. 2022, 143, 68–76. [Google Scholar] [CrossRef]
  99. Tao, Y.; Zhou, J.; Wang, Z.; Tao, H.; Bai, J.; Ge, G.; Li, W.; Zhang, W.; Hao, Y.; Yang, X.; et al. Human bone mesenchymal stem cells-derived exosomal miRNA-361-5p alleviates osteoarthritis by downregulating DDX20 and inactivating the NF-κB signaling pathway. Bioorganic Chem. 2021, 113, 104978. [Google Scholar] [CrossRef]
  100. Tavasolian, F.; Hosseini, A.Z.; Soudi, S.; Naderi, M. miRNA-146a Improves Immunomodulatory Effects of MSC-derived Exosomes in Rheumatoid Arthritis. Curr. Gene Ther. 2020, 20, 297–312. [Google Scholar] [CrossRef]
  101. Zheng, J.; Zhu, L.; In, I.I.; Chen, Y.; Jia, N.; Zhu, W. Bone marrow-derived mesenchymal stem cells-secreted exosomal microRNA-192-5p delays inflammatory response in rheumatoid arthritis. Int. Immunopharmacol. 2019, 78, 105985. [Google Scholar] [CrossRef] [PubMed]
  102. Gorczynski, R.M.; Zhu, F.; Chen, Z.; Kos, O.; Khatri, I. A comparison of serum miRNAs influencing metastatic growth of EMT6 vs 4THM tumor cells in wild-type and CD200R1KO mice. Breast Cancer Res. Treat. 2017, 162, 255–266. [Google Scholar] [CrossRef] [PubMed]
  103. Guo, J.; Duan, Z.; Zhang, C.; Wang, W.; He, H.; Liu, Y.; Wu, P.; Wang, S.; Song, M.; Chen, H.; et al. Mouse 4T1 Breast Cancer Cell–Derived Exosomes Induce Proinflammatory Cytokine Production in Macrophages via miR-183. J. Immunol. 2020, 205, 2916–2925. [Google Scholar] [CrossRef] [PubMed]
  104. Li, J.; Xu, P.; Wu, D.; Guan, M.; Weng, X.; Lu, Y.; Zeng, Y.; Chen, R. Hypoxic stress suppresses lung tumor-secreted exosomal miR101 to activate macrophages and induce inflammation. Cell Death Dis. 2021, 12, 1–11. [Google Scholar] [CrossRef]
  105. Van der Vos, K.E.; Abels, E.R.; Zhang, X.; Lai, C.; Carrizosa, E.; Oakley, D.; Prabhakar, S.; Mardini, O.; Crommentuijn, M.H.W.; Skog, J.; et al. Directly visualized glioblastoma-derived extracellular vesicles transfer RNA to microglia/macrophages in the brain. Neuro-Oncology 2016, 18, 58–69. [Google Scholar] [CrossRef] [Green Version]
  106. Wang, J.; Pei, B.; Yan, J.; Xu, X.; Fang, A.-N.; Ocansey, D.K.W.; Zhang, X.; Qian, H.; Xu, W.; Mao, F. hucMSC-Derived Exosomes Alleviate the Deterioration of Colitis via the miR-146a/SUMO1 Axis. Mol. Pharm. 2022, 19, 484–493. [Google Scholar] [CrossRef]
  107. Byun, J.-S.; Lee, H.Y.; Tian, J.; Moon, J.S.; Choi, J.; Lee, S.-H.; Kim, Y.-G.; Yi, H.-S. Effect of Salivary Exosomal miR-25-3p on Periodontitis with Insulin Resistance. Front. Immunol. 2022, 12, 775046. [Google Scholar] [CrossRef]
  108. Li, R.; Li, D.; Wang, H.; Chen, K.; Wang, S.; Xu, J.; Ji, P. Exosomes from adipose-derived stem cells regulate M1/M2 macrophage phenotypic polarization to promote bone healing via miR-451a/MIF. Stem Cell Res. Ther. 2022, 13, 149. [Google Scholar] [CrossRef]
  109. Liu, W.; Yu, M.; Chen, F.; Wang, L.; Ye, C.; Chen, Q.; Zhu, Q.; Xie, D.; Shao, M.; Yang, L. A novel delivery nanobiotechnology: Engineered miR-181b exosomes improved osteointegration by regulating macrophage polarization. J. Nanobiotechnology 2021, 19, 269. [Google Scholar] [CrossRef]
  110. Liu, W.; Zhou, N.; Liu, Y.; Zhang, W.; Li, X.; Wang, Y.; Zheng, R.; Zhang, Y. Mesenchymal stem cell exosome-derived miR-223 alleviates acute graft-versus-host disease via reducing the migration of donor T cells. Stem Cell Res. Ther. 2021, 12, 153. [Google Scholar] [CrossRef]
  111. Song, K.; Jiang, T.; Pan, P.; Yao, Y.; Jiang, Q. Exosomes from tendon derived stem cells promote tendon repair through miR-144-3p-regulated tenocyte proliferation and migration. Stem Cell Res. Ther. 2022, 13, 80. [Google Scholar] [CrossRef] [PubMed]
  112. Tsai, S.C.-S.; Yang, K.D.; Chang, K.-H.; Lin, F.C.-F.; Chou, R.-H.; Li, M.-C.; Cheng, C.-C.; Kao, C.-Y.; Chen, C.-P.; Lin, H.-C.; et al. Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice. Int. J. Mol. Sci. 2021, 22, 6664. [Google Scholar] [CrossRef] [PubMed]
  113. Wang, L.; Yin, P.; Wang, J.; Wang, Y.; Sun, Z.; Zhou, Y.; Guan, X. Delivery of mesenchymal stem cells-derived extracellular vesicles with enriched miR-185 inhibits progression of OPMD. Artif. Cells Nanomed. Biotechnol. 2019, 47, 2481–2491. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  114. Xu, J.; Xie, G.; Yang, W.; Wang, W.; Zuo, Z.; Wang, W. Platelet-rich plasma attenuates intervertebral disc degeneration via delivering miR-141-3p-containing exosomes. Cell Cycle 2021, 20, 1487–1499. [Google Scholar] [CrossRef] [PubMed]
  115. Yang, C.; Lim, W.; Park, J.; Park, S.; You, S.; Song, G. Anti-inflammatory effects of mesenchymal stem cell-derived exosomal microRNA-146a-5p and microRNA-548e-5p on human trophoblast cells. Mol. Hum. Reprod. 2019, 25, 755–771. [Google Scholar] [CrossRef]
  116. Zhang, Z.; Shuai, Y.; Zhou, F.; Yin, J.; Hu, J.; Guo, S.; Wang, Y.; Liu, W. PDLSCs Regulate Angiogenesis of Periodontal Ligaments via VEGF Transferred by Exosomes in Periodontitis. Int. J. Med. Sci. 2020, 17, 558–567. [Google Scholar] [CrossRef] [Green Version]
  117. Zhu, L.; Shi, Y.; Liu, L.; Wang, H.; Shen, P.; Yang, H. Mesenchymal stem cells-derived exosomes ameliorate nucleus pulposus cells apoptosis via delivering miR-142-3p: Therapeutic potential for intervertebral disc degenerative diseases. Cell Cycle 2020, 19, 1727–1739. [Google Scholar] [CrossRef]
Biomedicines 10 01601 g001 550
Figure 1. Flowchart of study selection.
Figure 1. Flowchart of study selection.
Biomedicines 10 01601 g001
Table
Table 1. Extracellular miRNAs in organ injury.
Table 1. Extracellular miRNAs in organ injury.
AuthorDiseaseSubjectEV TypeTargeted miRNAs
LiverBala et al. (2012) [23]Alcoholic liver diseaseMouseExomiR-122, miR-155,
Chen et al. (2018) [24]Autoimmune hepatitisMouseExomiR-223
Chen et al. (2018) [25]Liver fibrosisMouseEVmiR-34c, miR-151, miR-483, miR-532, miR-687
Liu et al. (2018) [26]Acute liver failureMouseExomiR-17
Liu et al. (2020) [27]Nonalcoholic fatty liver diseaseRatExomiR-192
Lu et al. (2019) [28]Autoimmune hepatitisMouseExomiR-223
Shao et al. (2020) [29]Acute liver injuryMouseExomiR-455
LungJiang et al. (2021) [30]Acute lung injuryMouseExomiR-125b
Liu et al. (2021) [31]Acute lung injuryMouseExomiR-384
Shen et al. (2022) [32]Septic lung injuryMouseExomiR-490
Tian et al. (2021) [33]Septic lung injuryMouseExomiR-16
Wei et al. (2020) [34]Acute lung injuryMouseExomiR-377
Zhang et al. (2019) [35]Lung inflammationMouseMVmiR-223, miR-142
Zheng et al. (2021) [36]Acute lung injuryRatExomiR-22
HeartChen et al. (2017) [37]Myocardial infarctionRatExomiR-133
Kwon et al. (2021) [38]Myocardial infarctionRatEVmiR-7004, mi7-7b
Luo et al. (2017) [39]Acute myocardial infarctionRatExomiR-126
Milano et al. (2020) [40]CardiotoxicityRatExomiR-146a
Pan et al. (2019) [41]Myocardial infarctionRatExomiR-146a
Peng et al. (2020) [42]Myocardial infarctionMouseExomiR-25
Sun et al. (2022) [43]Sepsis induced myocardial infarctionMouseExomiR-24
Wang et al. (2015) [44]Sepsis induced myocardial dysfunctionMouseExomiR-223
Wang et al. (2022) [45]Myocardial infractionMouseExomiR-129
Yu et al. (2021) [46]Cardiac hypertrophyRatExomiR-155
BowelCai et al. (2021) [47]ColitisMouseExomiR-378a
Deng et al. (2021) [48]Ulcerative colitisMouseExomiR-590
Lu et al. (2021) [49]Ulcerative colitisMouseExomiR-21a
Sun et al. (2020) [50]Inflammation-injured IECRatExomiR-200b
KidneyLi et al. (2019) [51]Tubulointerstitial inflammationMouseExomiR-23a
Li et al. (2020) [52]Ischemia/reperfusion injuryRatExomiR-146a
Li et al. (2020) [53]Diabetic kidney diseasesMouseExomiR-26a
Pan et al. (2019) [54]Sepsis, Acute kidney injuryMouseExomiR-21
Other organsJimenez-Alesanco et al. (2019) [55]Acute pancreatitisRatExomiR-155
Liang et al. (2019) [56]Urethral strictureRatExomiR-146a
Liu et al. (2021) [57]Intrauterine adhesionMouseExomiR-223
Exo: exosome; EV: extracellular vesicle; MV: micro vesicle.
Table
Table 2. Extracellular miRNAs in immune dysfunction.
Table 2. Extracellular miRNAs in immune dysfunction.
AuthorDiseaseSubjectEV TypeTargeted miRNAs
Alexander et al. (2017) [58]Chronic inflammationMouseExomiR-155
Appiah et al. (2021) [59]SepsisMouseEVmiR-146a, miR-9, and miR-155
Balusu et al. (2016) [60]Systemic inflammatory diseasesMouseEVmiR-1a, miR-9, miR-146a, miR-155
Fernández-Messina et al. (2020) [61]Immune diseasesMouseEVmiR-20a, miR-25, miR-155
Gao et al. (2021) [62]SepsisRatExomiR-1
Li et al. (2021) [63]AsthmaMouseExomiR-370
Okoye et al. (2014) [64]Systemic diseaseMouseExolet-7d
Shan et al. (2022) [65]AsthmaMouseExomiR-188
Song et al. (2017) [66]SepsisMouseExomiR-146a
Yue et al. (2017) [67]Systemic inflammationMouseExomiR-375
Exo: exosome; EV: extracellular vesicle.
Table
Table 3. Extracellular miRNAs in neurological disease.
Table 3. Extracellular miRNAs in neurological disease.
AuthorDiseaseSubjectEV TypeTargeted miRNAs
Cai et al. (2021) [68]Ischemic strokeMouseExomiR-542
Fang et al. (2020) [69]DepressionRatExomiR-455, miR-126a, miR-122, miR-1b
Giunti et al. (2021) [70]NeuroinflammationMouseExomiR-467f, miR-466q
Huang et al. (2018) [71]Traumatic brain injury—neuronal inflammationMouseExomiR-124
Li et al. (2018) [72]NeuroinflammationMouseExomiR-21, miR-125a, miR-146a, miR-155
Li et al. (2020) [73]DepressionMouseExomiR-207
Li et al. (2020) [74]Spinal cord injuryRatExomiR-544
Ma et al. (2019) [75]Spinal cord injuryRatExomiR-219a-2
Simeoli et al. (2017) [76]Neuropathic painMouseExomiR-21-5p, miR-21
Song et al. (2019) [77]Ischemic brain injuryRatExomiR-181c
Xiaoying et al. (2020) [78]EpilepsyMouseExomiR-181a
Yang et al. (2021) [79]Alzheimer’s diseaseMouseExomiR-146a
Zhai et al. (2021) [80]Alzheimer’s diseaseMouseExomiR-22
Exo: exosome; EV: extracellular vesicle.
Table
Table 4. Extracellular miRNAs in metabolic syndrome.
Table 4. Extracellular miRNAs in metabolic syndrome.
AuthorDiseaseSubjectEV TypemiRNAs
Huang et al. (2021) [81]Ischemic disease—diabetic footRatExomiR-21
Lakhter et al. (2018) [82]Type 1 diabetesMouseEVmiR-21
Li et al. (2021) [83]Diabetic retinopathyMouseExomiR-17
Pan et al. (2019) [84]Obesity-induced metabolic inflammationMouseExomiR-34a
Resaz et al. (2020) [85]Glycogen storage disease type 1aMouseExolet-7d, miR-142, let-7i, miR-145a, miR-150, miR-15b, miR-192, miR-21a, miR-29a, miR-342, miR-345, miR-409, miR-486a, miR-744
Sun et al. (2021) [86]Type 2 diabetes mellitusMouseExomiR-29
Ying et al. (2021) [87]ObesityMouseExomiR-690
Exo: exosome; EV: extracellular vesicle.
Table
Table 5. Extracellular miRNAs in vesicular disease.
Table 5. Extracellular miRNAs in vesicular disease.
AuthorDiseaseSubjectEV TypemiRNAs
Bai et al. (2020) [88]AtherosclerosisMouseExomiR-21a, miR-222, miR-221, miR-155, miR-29a, miR-199a, miR-146a
Bu et al. (2021) [89]AtherosclerosisMouseExomiR-155
Chen et al. (2021) [90]AtherosclerosisMouseExomiR-512
Gao et al. (2021) [91]AtherosclerosisMouseExomiR-100
Lee et al. (2012) [92]Pulmonary hypertensionMouseExomiR-204
Li et al. (2019) [93]AtherosclerosisMouseExolet-7
Zhang et al. (2019) [94]AtherosclerosisRatExomiR-146a
Zhang et al. (2021) [95]Coronary artery diseaseRatExomiR-98
Exo: exosome; EV: extracellular vesicle.
Table
Table 6. Extracellular miRNAs in arthritis.
Table 6. Extracellular miRNAs in arthritis.
AuthorDiseaseSubjectEV TypemiRNAs
Donate et al. (2021) [96]Rheumatoid arthritisMouseEVmiR-132
Huang et al. (2021) [97]OsteoarthritisMouseExomiR-206
Huang et al. (2022) [98]Rheumatoid arthritisRatExomiR-223
Tao et al. (2021) [99]OsteoarthritisRatExomiR-361
Tavasolian et al. (2020) [100]Rheumatoid arthritisMouseExomiR-146a, miR-155
Zheng et al. (2020) [101]Rheumatoid arthritisRatExomiR-192
Exo: exosome; EV: extracellular vesicle.
Table
Table 7. Extracellular miRNAs in cancer.
Table 7. Extracellular miRNAs in cancer.
AuthorDiseaseSubjectEV TypemiRNAs
Gorczynski et al. (2017) [102]Breast cancerMouseExomiR-155, miR-205
Guo et al. (2020) [103]Breast cancerMouseExomiR-183
Li et al. (2021) [104]Lung cancerMouseExomiR-101
Van der Vos et al. (2016) [105]GlioblastomaMouseEVmiR-21
Wang et al. (2022) [106]Colorectal cancerMouseExomiR-146a
Exo: exosome; EV: extracellular vesicle.
Table
Table 8. Extracellular miRNAs in other inflammatory disease model.
Table 8. Extracellular miRNAs in other inflammatory disease model.
AuthorDiseaseSubjectEV TypemiRNAs
Byun et al. (2022) [107]PeriodontitisMouseExomiR-25
Li et al. (2022) [108]Traumatic bone defectsRatExomiR-451a
Liu et al. (2021) [109]Aseptic loosening and poor osteointegrationMouse/ratExomiR-181b
Liu et al. (2021) [110]Acute graft-versus-host diseaseMouseExomiR-223
Song et al. (2022) [111]Tendon pathologiesRatExomiR-144
Tsai et al. (2021) [112]Ototoxicity-induced hearing lossMouseExomiR-125a, miR-125b, miR-127
Wang et al. (2019) [113]OPMDHamsterEVmiR-185
Xu et al. (2021) [114]Intervertebral disc degenerationMouseExomiR-141
Yang et al. (2019) [115]Placental oxidative stress, preterm birthMouseExomiR-146a, miR-548e
Zhang et al. (2020) [116]PeriodontitisRatExomiR-17
Zhu et al. (2020) [117] Intervertebral disc degenerationMouseExomiR-142
Exo: exosome; EV: extracellular vesicle.
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Lee, S.; Ko, J.H.; Kim, S.-N. The Extracellular MicroRNAs on Inflammation: A Literature Review of Rodent Studies. Biomedicines 2022, 10, 1601. https://doi.org/10.3390/biomedicines10071601

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Lee S, Ko JH, Kim S-N. The Extracellular MicroRNAs on Inflammation: A Literature Review of Rodent Studies. Biomedicines. 2022; 10(7):1601. https://doi.org/10.3390/biomedicines10071601

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Lee, Seri, Jade Heejae Ko, and Seung-Nam Kim. 2022. "The Extracellular MicroRNAs on Inflammation: A Literature Review of Rodent Studies" Biomedicines 10, no. 7: 1601. https://doi.org/10.3390/biomedicines10071601

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Lee, S., Ko, J. H., & Kim, S.-N. (2022). The Extracellular MicroRNAs on Inflammation: A Literature Review of Rodent Studies. Biomedicines, 10(7), 1601. https://doi.org/10.3390/biomedicines10071601

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