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Extracellular Vesicles in Human Diseases

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 13121

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Prof. Dr. Qianyun Xi

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Guest Editor

College of Animal Science, South China Agricultural University, 483 Wushan Road, Guangzhou 510642, China
Interests: MiRNAs; extracellular vesicles; exosomes; mammalian growth; reproduction; glucose and lipid metabolism, protein metabolism; signal pathways, regulation of gene expression, epigenetics

Special Issue Information

Dear Colleagues,

Extracellular vesicles (EVs) have the potential to identify unknown cellular and molecular mechanisms, which play important roles in cell-to-cell communication, organ homeostasis and disease. EVS are generally divided into two broad categories: ectosomes and exosomes. Ectosomes are vesicles produced by the direct germination of the plasma membrane, which produces microvesicles, microparticles and large vesicles about 50 nm to 1 mm in diameter. In contrast, exosomes are endosome-derived and range in diameter from about 40 to 160 NM (mean: approximately 100 nm). A variety of cells and body fluids can secrete exosomes, including endothelial cells, immune cells, platelets, smooth muscle cells, and so on. When they are secreted by host cells into recipient cells, exosomes can regulate the biological activity of recipient cells by carrying proteins, nucleic acids, lipids and so on. The application potential of EV in mammalian reproduction and development, immune response and infection, substance metabolism, cardiovascular disease, neurodegeneration, cancer, etc., have encouraged major research advances in this field.

Prof. Dr. Qianyun Xi
Guest Editor

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Published Papers (5 papers)

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Research

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14 pages, 3234 KiB

Open AccessArticle

Distribution of Signal Peptides in Microvesicles from Activated Macrophage Cells

by Kenji Ono, Junpei Sato, Hiromi Suzuki and Makoto Sawada

Int. J. Mol. Sci. 2023, 24(15), 12131; https://doi.org/10.3390/ijms241512131 - 28 Jul 2023

Viewed by 828

Abstract

Extracellular vesicles, such as microvesicles (LEV) and exosomes (SEV), play an important role in intercellular signaling by encapsulating functional molecules and delivering them to specific cells. Recent studies showed that signal peptides (SPs), which are derived from sequences at the N-terminal of newly synthesized proteins, exhibited biological activity in the extracellular fluid. We previously reported that SPs were secreted into the extracellular fluid via SEV; however, it remains unclear whether the release of SPs occurs via LEV. In the present study, we demonstrated that SP fragments from human placental secreted alkaline phosphatase (SEAP) were present in LEV as well as SEV released from RAW-Blue cells, which stably express an NF-κB-inducible SEAP reporter. When RAW-Blue cells were treated with LPS at 0–10,000 ng/mL, SEAP SP fragments per particle were more abundant in LEV than in SEV, with fragments in LEV and SEV reaching a maximum at 1000 and 100 ng/mL, respectively. The content of SEAP SP fragments in LEV from IFNγ-stimulated RAW-Blue cells was higher than those from TNFα-stimulated cells, whereas that in SEV from TNFα-stimulated RAW-Blue cells was higher than those from IFNγ−stimulated cells. Moreover, the content of SEAP SP fragments in LEV and SEV decreased in the presence of W13, a calmodulin inhibitor. Collectively, these results indicate that the transportation of SP fragments to extracellular vesicles was changed by cellular activation, and calmodulin was involved in their transportation to LEV and SEV. Full article

(This article belongs to the Special Issue Extracellular Vesicles in Human Diseases)

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20 pages, 12534 KiB

Open AccessArticle

Skeletal Muscle-Derived Exosomal miR-146a-5p Inhibits Adipogenesis by Mediating Muscle-Fat Axis and Targeting GDF5-PPARγ Signaling

by Mengran Qin, Lipeng Xing, Jiahan Wu, Shulei Wen, Junyi Luo, Ting Chen, Yaotian Fan, Jiahao Zhu, Lekai Yang, Jie Liu, Jiali Xiong, Xingping Chen, Canjun Zhu, Songbo Wang, Lina Wang, Gang Shu, Qingyan Jiang, Yongliang Zhang, Jiajie Sun and Qianyun Xi

Int. J. Mol. Sci. 2023, 24(5), 4561; https://doi.org/10.3390/ijms24054561 - 25 Feb 2023

Cited by 7 | Viewed by 2316

Abstract

Skeletal muscle-fat interaction is essential for maintaining organismal energy homeostasis and managing obesity by secreting cytokines and exosomes, but the role of the latter as a new mediator in inter-tissue communication remains unclear. Recently, we discovered that miR-146a-5p was mainly enriched in skeletal muscle-derived exosomes (SKM-Exos), 50-fold higher than in fat exosomes. Here, we investigated the role of skeletal muscle-derived exosomes regulating lipid metabolism in adipose tissue by delivering miR-146a-5p. The results showed that skeletal muscle cell-derived exosomes significantly inhibited the differentiation of preadipocytes and their adipogenesis. When the skeletal muscle-derived exosomes co-treated adipocytes with miR-146a-5p inhibitor, this inhibition was reversed. Additionally, skeletal muscle-specific knockout miR-146a-5p (mKO) mice significantly increased body weight gain and decreased oxidative metabolism. On the other hand, the internalization of this miRNA into the mKO mice by injecting skeletal muscle-derived exosomes from the Flox mice (Flox-Exos) resulted in significant phenotypic reversion, including down-regulation of genes and proteins involved in adipogenesis. Mechanistically, miR-146a-5p has also been demonstrated to function as a negative regulator of peroxisome proliferator-activated receptor γ (PPARγ) signaling by directly targeting growth and differentiation factor 5 (GDF5) gene to mediate adipogenesis and fatty acid absorption. Taken together, these data provide new insights into the role of miR-146a-5p as a novel myokine involved in the regulation of adipogenesis and obesity via mediating the skeletal muscle-fat signaling axis, which may serve as a target for the development of therapies against metabolic diseases, such as obesity. Full article

(This article belongs to the Special Issue Extracellular Vesicles in Human Diseases)

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22 pages, 6372 KiB

Open AccessArticle

Approaches for sRNA Analysis of Human RNA-Seq Data: Comparison, Benchmarking

by Vitalik Bezuglov, Alexey Stupnikov, Ivan Skakov, Victoria Shtratnikova, J. Richard Pilsner, Alexander Suvorov and Oleg Sergeyev

Int. J. Mol. Sci. 2023, 24(4), 4195; https://doi.org/10.3390/ijms24044195 - 20 Feb 2023

Cited by 2 | Viewed by 2508

Abstract

Expression analysis of small noncoding RNA (sRNA), including microRNA, piwi-interacting RNA, small rRNA-derived RNA, and tRNA-derived small RNA, is a novel and quickly developing field. Despite a range of proposed approaches, selecting and adapting a particular pipeline for transcriptomic analysis of sRNA remains a challenge. This paper focuses on the identification of the optimal pipeline configurations for each step of human sRNA analysis, including reads trimming, filtering, mapping, transcript abundance quantification and differential expression analysis. Based on our study, we suggest the following parameters for the analysis of human sRNA in relation to categorical analyses with two groups of biosamples: (1) trimming with the lower length bound = 15 and the upper length bound = Read length − 40% Adapter length; (2) mapping on a reference genome with bowtie aligner with one mismatch allowed (-v 1 parameter); (3) filtering by mean threshold > 5; (4) analyzing differential expression with DESeq2 with adjusted p-value < 0.05 or limma with p-value < 0.05 if there is very little signal and few transcripts. Full article

(This article belongs to the Special Issue Extracellular Vesicles in Human Diseases)

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15 pages, 2580 KiB

Open AccessArticle

Analyses of circRNA Expression throughout the Light-Dark Cycle Reveal a Strong Regulation of Cdr1as, Associated with Light Entrainment in the SCN

by Andranik Ivanov, Daniele Mattei, Kathrin Radscheit, Anne-Claire Compagnion, Jan Patrick Pett, Hanspeter Herzel, Rosa Chiara Paolicelli, Monika Piwecka, Urs Meyer and Dieter Beule

Int. J. Mol. Sci. 2022, 23(20), 12347; https://doi.org/10.3390/ijms232012347 - 15 Oct 2022

Cited by 3 | Viewed by 2452

Abstract

Circular RNAs (circRNAs) are a large class of relatively stable RNA molecules that are highly expressed in animal brains. Many circRNAs have been associated with CNS disorders accompanied by an aberrant wake-sleep cycle. However, the regulation of circRNAs in brain homeostasis over daily light-dark (LD) cycles has not been characterized. Here, we aim to quantify the daily expression changes of circRNAs in physiological conditions in healthy adult animals. Using newly generated and public RNA-Seq data, we monitored circRNA expression throughout the 12:12 h LD cycle in various mouse brain regions. We identified that Cdr1as, a conserved circRNA that regulates synaptic transmission, is highly expressed in the suprachiasmatic nucleus (SCN), the master circadian pacemaker. Despite its high stability, Cdr1as has a very dynamic expression in the SCN throughout the LD cycle, as well as a significant regulation in the hippocampus following the entry into the dark phase. Computational integration of different public datasets predicted that Cdr1as is important for regulating light entrainment in the SCN. We hypothesize that the expression changes of Cdr1as in the SCN, particularly during the dark phase, are associated with light-induced phase shifts. Importantly, our work revises the current beliefs about natural circRNA stability and suggests that the time component must be considered when studying circRNA regulation. Full article

(This article belongs to the Special Issue Extracellular Vesicles in Human Diseases)

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Review

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13 pages, 797 KiB

Open AccessReview

Naming the Barriers between Anti-CCR5 Therapy, Breast Cancer and Its Microenvironment

by Elizabeth Brett, Dominik Duscher, Andrea Pagani, Adrien Daigeler, Jonas Kolbenschlag and Markus Hahn

Int. J. Mol. Sci. 2022, 23(22), 14159; https://doi.org/10.3390/ijms232214159 - 16 Nov 2022

Cited by 7 | Viewed by 4464

Abstract

Breast cancer represents the most common malignancy among women in the world. Although immuno-, chemo- and radiation therapy are widely recognized as the therapeutic trifecta, new strategies in the fight against breast cancer are continually explored. The local microenvironment around the tumor plays a great role in cancer progression and invasion, representing a promising therapeutic target. CCL5 is a potent chemokine with a physiological role of immune cell attraction and has gained particular attention in R&D for breast cancer treatment. Its receptor, CCR5, is a well-known co-factor for HIV entry through the cell membrane. Interestingly, biology research is unusually unified in describing CCL5 as a pro-oncogenic factor, especially in breast cancer. In silico, in vitro and in vivo studies blocking the CCL5/CCR5 axis show cancer cells become less invasive and less malignant, and the extracellular matrices produced are less oncogenic. At present, CCR5 blocking is a mainstay of HIV treatment, but despite its promising role in cancer treatment, CCR5 blocking in breast cancer remains unperformed. This review presents the role of the CCL5/CCR5 axis and its effector mechanisms, and names the most prominent hurdles for the clinical adoption of anti-CCR5 drugs in cancer. Full article

(This article belongs to the Special Issue Extracellular Vesicles in Human Diseases)

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