Extracellular Vesicles in Renal Inflammatory Diseases: Revealing Mechanisms of Extracellular Vesicle-Mediated Macrophage Regulation
Abstract
1. Introduction
2. Macrophages and EVs in the Kidney
2.1. Origin of Macrophages in the Kidney
2.2. Plasticity and Polarization of Macrophages in the Kidney
2.3. EVs and Kidney Disease
3. EV-Mediated Macrophage Regulation in AKI
3.1. Ischemia/Reperfusion AKI (I/R-AKI)
3.2. Sepsis-Induced AKI (S-AKI)
3.3. Cisplatin-Induced AKI (CI-AKI)
3.4. EVs as Diagnostic Biomarkers for AKI
3.5. AKI Therapeutic Strategies Targeting EV-Regulated Macrophages
4. EV-Mediated Macrophage Regulation in CKD
4.1. Kidney Fibrosis
4.2. Diabetic Nephropathy (DN)
4.3. Lupus Nephritis (LN)
4.4. EVs as Diagnostic Biomarkers for CKD
4.5. CKD Therapeutic Strategies Targeting EV-Regulated Macrophages
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Origin | Product | Mechanism | Creature | References |
---|---|---|---|---|
MSCs | IDO | Regulation of macrophage polarization to M2-type promotes kidney self-repair in IRI | Mouse | [104] |
Huc-MSCs | Unknown | Reduction in macrophage infiltration inhibits kidney inflammation, inhibits tubular cell apoptosis | Pig | [105] |
Huc-MSCs | Unknown | Upregulation of miR-146b level reduces IRAK1 expression and inhibits NF-κB activity to suppress the secretion of inflammatory mediators by M1-type macrophages | Mouse | [46] |
MSCs | CCR2 | Reduce the concentration of free CCL2 to inhibit its recruitment and activation of macrophages | Mouse | [70] |
MSCs | miR-100-5p | Targeting the FKBP5/AKT axis promotes M1 to M2 macrophage transformation and inhibits TEC apoptosis | Human being | [106] |
USCs | miR-146a-5p | Targeted downregulation of IRAK-1 inhibits M1 macrophage polarization and attenuates HK-2 cell apoptosis | Human being | [107] |
USCs | let-7b-5p | Targeting TLR4/NF-κB/STAT3/AKT promotes M2-type macrophage polarization | Human being | [108] |
MSCs | miR-21 | Targeting PDCD4 promotes M2 polarization | Mouse | [109] |
hAECs | Multiple proteins | Reduction in macrophage infiltration to inhibit TNF-α production and ultimately suppress TNF α-induced inflammatory response and tubular cell apoptosis | Mouse | [110] |
MSCs | miR-27b | Targeting the JMJD3/NF-κB/p6 axis to inhibit macrophage inflammation and reduce kidney injury | Mouse | [111] |
Unknown | miR-30c-5p | Promotion of M1 macrophages transforming to M2 to attenuate kidney I/R injury | Rat | [112] |
TECs | miR-20a-5p | Inhibition of macrophage infiltration prevents acute tubular injury | Mouse | [113] |
ASCs | Unknown | Promotion of macrophage polarizing to M2-type to increase phagocytosis and inhibit TEC death | Human being | [114] |
Macrophages (M2 > M1) | miR-93-5p | Regulation of miR-93/TXNIP signaling pathway inhibits TEC’s pyroptosis | Mouse | [79] |
Macrophage | IL-10 | Inhibition of mTOR signaling induces mitochondrial autophagy and promotes M2 polarization | Mouse | [115] |
SCAP | Biologically active compound | Inhibition of oxidative stress, inflammation, and apoptosis to protect TECs | Rat | [89] |
Origin | Product | Mechanism | Creature | References |
---|---|---|---|---|
BMSCs | Unknown | Activate EP2 receptors and reduce the number of M1 and M2 macrophages to inhibit MMT process and alleviate renal fibrosis | UUO-Mouse | [170] |
BMSCs | miR-204-5p | Regulation of the PI3K-AKT pathway affects autophagy, inhibits M1-type polarization, and promotes M2-type polarization | Mouse | [171] |
Huc-MSCs | Unknown | Inhibition of kidney fibrosis by blocking the MMT process through the inhibition of ARNTL expression | UUO-Mouse | [172] |
Huc-MSCs | miR-146a-5p | Targeting TRAF6 to promote M2-type macrophage polarization alleviates kidney impairment in DN | Human being | [173] |
MSCs | miR-486-5p | Targeting PIK3R1 via the PI3K/Akt pathway promotes M2-type macrophage polarization and prevents diabetic nephropathy | Mouse | [174] |
USCs | circRNA ATG7 | Regulation of the SOCS1/STAT3 pathway by miR-4500 promotes macrophage polarization from M1 to M2 to inhibit DN progression | Human being | [175] |
M2-type macrophage | miR-93-5p | Activation of autophagy by inhibiting DUSP1 expression ameliorates HG-induced podocyte damage | Mouse | [176] |
M2-type macrophage | miR-25-3p | Targeting TLR4 attenuates podocyte apoptosis or upregulates ATXN3 expression to promote podocyte proliferation | Mouse | [162,177] |
M1-type macrophage | miR-21a-5p | Inhibition of Tnpo1 expression in podocytes attenuates podocyte damage in HG | Mouse | [162] |
Huc-MSCs | Unknown | Alleviation of podocyte injury in LN by promoting M2-type macrophage polarization | Human being | [178] |
BMSCs | miR-16 | Attenuation of lupus nephritis by regulating PDCD4 pathway to induce M2-type macrophage polarization | Mouse | [179] |
BMSCs | miR-21 | Alleviation of lupus nephritis by regulating PTEN pathway to induce M2-type macrophage polarization | Mouse | [179] |
Unknown | LNA-anti-miR-150 | Inhibition of M1 macrophage infiltration by targeting SOCS1 to attenuate LN-induced kidney injury | Mouse | [180] |
Kidney Disease | Urinary EV Product | Number Enrolled/Animal Model | Results | References |
---|---|---|---|---|
AKI | Fetuin-A | 3 healthy volunteers 3 ICU patients with CI-AKI 3 ICU patients without AKI | Patients in the ICU with CI-AKI show a significant increase in Fetuin-A levels. | [186] |
AKI | ATF3 | S-AKI patients (n = 8) and healthy controls (n = 8) | Compared to healthy volunteers, S-AKI patients have higher levels of uATF3, which is negative in all the healthy volunteers. | [198] |
AKI | Aquaporin-1 | Renal ischemia/reperfusion rat model | Urinary vesicle aquaporin-1 abundance reduction emerges. | [199] |
AKI | miR-16 | Rat model of I/R-AKI | miR-16 expression is increased in UEs. | [200] |
CKD | Ceruloplasmin | CKD (n = 15) and controls (n = 15) | Elevated urinary vesicle Ceruloplasmin was observed prior to proteinuria. | [201] |
CKD | Osteoprotegerin | CKD (n = 14) and healthy controls (n = 4) | Urinary vesicle protein Osteoprotegerin levels are higher in patients with CKD than in healthy volunteers. | [202] |
CKD | WT1 | Type-1 diabetes mellitus patients (n = 48) patients and healthy controls (n = 25) | The WT1 protein is predominantly present in UE of diabetic patients, with its expression levels increasing as kidney function declines. | [191,194] |
CKD | CD63 | Microalbuminuria-stage DN patients (n = 62) and controls (n = 29) | During the early stages of DN, the content of EVs containing CD63 in urine significantly increased. | [203] |
CKD | E-cadherin | 27 prevalent case-patients with posterior urethral valves and 20 age-matched controls | Patients excrete significantly lower levels of E-cadherin. | [204] |
CKD | TGF-B1 | 27 prevalent case-patients with posterior urethral valves and 20 age-matched controls | Patients excrete significantly higher levels of TGF-B1. | [204] |
CKD | N-cadherin | 27 prevalent case-patients with posterior urethral valves and 20 age-matched controls | Patients excrete significantly lower levels of N-cadherin. | [204] |
CKD | L1CAM | 27 prevalent case-patients with posterior urethral valves and 20 age-matched controls | Patients excrete significantly higher levels of L1CAM. | [204] |
CKD | miR-192 | 80 patients diagnosed with Type-2 diabetes (30 normoal buminuria, 30 microalbuminuria, and 20 macroalbuminuria) and 10 healthy controls | miR-192 is better than miR-194 and miR-215 in identifying DN in patients with normoal buminuria or microalbuminuria, which indicated that uEVs miR-192 might be able to diagnose DN earlier. | [205] |
CKD | miR-15a-5p | 40 patients with type-2 diabetes mellitus (T2DM) patients, 20 patients with normoal buminuria, and 20 patients with macroalbuminuria | miR-15a-5p is downregulated in DN patients compared to T2DM patients. | [206] |
CKD | miR-29c | 45 LN patients and 20 healthy/LN (n = 32), nonlupus CKD patients (n = 15) and healthy controls (n = 20) | In patients with LN, urinary vesicle miR-29c may serve as a potential biomarker for predicting disease progression. | [197,207] |
CKD | miR-200b/miR-200 | 38 CKD patients with different degrees of renal fibrosis and in 12 normal individuals/32 CKD patients and 7 controls | The level of miR-200b in the CKD group is lower and negatively correlated with fibrosis | [208] |
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Wei, J.; Xie, Z.; Kuang, X. Extracellular Vesicles in Renal Inflammatory Diseases: Revealing Mechanisms of Extracellular Vesicle-Mediated Macrophage Regulation. Int. J. Mol. Sci. 2025, 26, 3646. https://doi.org/10.3390/ijms26083646
Wei J, Xie Z, Kuang X. Extracellular Vesicles in Renal Inflammatory Diseases: Revealing Mechanisms of Extracellular Vesicle-Mediated Macrophage Regulation. International Journal of Molecular Sciences. 2025; 26(8):3646. https://doi.org/10.3390/ijms26083646
Chicago/Turabian StyleWei, Jiatai, Zijie Xie, and Xiaodong Kuang. 2025. "Extracellular Vesicles in Renal Inflammatory Diseases: Revealing Mechanisms of Extracellular Vesicle-Mediated Macrophage Regulation" International Journal of Molecular Sciences 26, no. 8: 3646. https://doi.org/10.3390/ijms26083646
APA StyleWei, J., Xie, Z., & Kuang, X. (2025). Extracellular Vesicles in Renal Inflammatory Diseases: Revealing Mechanisms of Extracellular Vesicle-Mediated Macrophage Regulation. International Journal of Molecular Sciences, 26(8), 3646. https://doi.org/10.3390/ijms26083646