MicroRNAs of Equine Amniotic Mesenchymal Cell-derived Microvesicles and Their Involvement in Anti-inflammatory Processes.
Abstract: Cell-derived microvesicles (MVs) are a recently discovered mechanism of cell-to-cell communication. Our previous data show that MVs secreted by equine amniotic mesenchymal-derived cells (AMCs) are involved in downregulation of proinflammatory genes in lipopolysaccharide-stressed equine tendon and endometrial cells. The aim of the present study was to evaluate whether AMC-MVs contain selected microRNAs (miRNAs) involved in inflammation. Two pools of cells, derived from 3 amniotic membranes each, and their respective MVs were collected. Small RNAs were extracted and deep sequenced, followed by miRNA in silico detection. The analysis identified 1,285 miRNAs, which were quantified both in AMCs and MVs. Among these miRNAs, 401 were classified as Equus caballus miRNAs, 257 were predicted by homology with other species (cow, sheep, and goat), and 627 were novel candidate miRNAs. Moreover, 146 miRNAs differentially expressed (DE) in AMCs and MVs were identified, 36 of which were known and the remaining were novel. Among the known DE miRNAs, 17 showed higher expression in MVs. Three of these were validated by real time polymerase chain reaction: eca-miR-26, eca-miR-146a, and eca-miR-223. Gene ontology analysis of validated targets showed that the DE miRNAs in cells and MVs could be involved both in immune system regulation by modulating interleukin signaling and in the inflammatory process. In conclusion, this study suggests a significant role of AMCs in modulating immune response through cell-cell communication via MV-shuttling miRNAs.
Publication Date: 2018-03-23 PubMed ID: 29562776PubMed Central: PMC6434479DOI: 10.1177/0963689717724796Google Scholar: Lookup
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Summary
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This research explores how cell-derived microvesicles, specifically those secreted by equine amniotic mesenchymal cells, are involved in reducing inflammation. Using in-depth sequencing analysis, the study identifies over a thousand microRNAs within these microvesicles, many of which play roles in controlling immune response and inflammation.
Understanding Cell-derived Microvesicles and microRNAs
- Cell-derived microvesicles (MVs) are little packets released by cells, which have been recognized as a new way that cells communicate amongst each other. This communication is facilitated through the exchange of different molecules carried inside the MVs, including microRNAs (miRNAs).
- MiRNAs are small, non-coding RNA molecules that control gene expression. They can either upregulate or downregulate the functionality of certain genes, effectively playing a role in controlling various biological processes including inflammation.
The Study and Its Findings
- The research used equine amniotic mesenchymal-derived cells (AMCs) and the MVs they secreted, previously shown to be involved in suppressing inflammatory genes in other cells exposed to harmful substances.
- Using an in-depth sequencing technique called “deep sequencing”, the researchers examined the small RNAs present in both the AMCs and the MVs they release.
- The analysis revealed the presence of 1,285 miRNAs, classified further into three categories based on origin and nature: 401 described previously in horses, 257 predicted from similar sequences in other species, and 627 novel candidates.
- The researchers found 146 miRNAs that were differentially expressed between the AMCs and MVs, with 17 known miRNAs showing higher expressions in MVs. Three of these, eca-miR-26, eca-miR-146a, and eca-miR-223, were validated through an additional laboratory technique.
- The roles of these differentially expressed miRNAs were investigated, revealing involvement in immune system regulation, particularly in modulating signals from interleukin, a type of immune signaling molecule.
Implications of the Study
- The study concludes that AMCs might play a significant part in controlling immune responses and inflammation by transporting selected miRNAs via MVs.
- This discovery could potentially open new avenues for understanding and treating inflammatory conditions such as arthritis or allergies, where the immune response plays a crucial role.
- The uncovering of new miRNA candidates also points towards unexplored layers of cellular communication and regulation mechanisms.
Cite This Article
APA
Lange-Consiglio A, Lazzari B, Perrini C, Pizzi F, Stella A, Cremonesi F, Capra E.
(2018).
MicroRNAs of Equine Amniotic Mesenchymal Cell-derived Microvesicles and Their Involvement in Anti-inflammatory Processes.
Cell Transplant, 27(1), 45-54.
https://doi.org/10.1177/0963689717724796 Publication
Researcher Affiliations
- 1 Reproduction Unit, Centro Clinico-Veterinario e Zootecnico-Sperimentale di Ateneo, Università degli Studi di Milano, Lodi, Italy.
- 2 Parco Tecnologico Padano, Lodi, Italy.
- 3 Istituto di Biologia e Biotecnologia Agraria, Consiglio Nazionale delle Ricerche IBBA CNR, Lodi, Italy.
- 4 Department of Veterinary Medicine, Università degli Studi di Milano, Milano, Italy.
- 3 Istituto di Biologia e Biotecnologia Agraria, Consiglio Nazionale delle Ricerche IBBA CNR, Lodi, Italy.
- 2 Parco Tecnologico Padano, Lodi, Italy.
- 3 Istituto di Biologia e Biotecnologia Agraria, Consiglio Nazionale delle Ricerche IBBA CNR, Lodi, Italy.
- 1 Reproduction Unit, Centro Clinico-Veterinario e Zootecnico-Sperimentale di Ateneo, Università degli Studi di Milano, Lodi, Italy.
- 4 Department of Veterinary Medicine, Università degli Studi di Milano, Milano, Italy.
- 3 Istituto di Biologia e Biotecnologia Agraria, Consiglio Nazionale delle Ricerche IBBA CNR, Lodi, Italy.
MeSH Terms
- Amnion / immunology
- Amnion / metabolism
- Animals
- Cell Communication / drug effects
- Cell Communication / genetics
- Cell-Derived Microparticles / drug effects
- Cell-Derived Microparticles / metabolism
- Horses
- Lipopolysaccharides / pharmacology
- MicroRNAs / genetics
- MicroRNAs / metabolism
Conflict of Interest Statement
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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