ORIGINAL RESEARCH article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1542008
The function and mechanisms of UC-MSCs-derived exosomal miR-486-5p in pumonary fibrosis
Provisionally accepted
- 1Qinghai Provincial People's Hospital, Xining, China
- 2Ningbo No.2 hospital, Ningbo, Zhejiang Province, China
- 3Taian 88 hospital, Shandong, China
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Background: Currently, nintedanib and pirfenidone are the two primary pharmacological agents utilized for the treatment of pulmonary fibrosis (PF). However, neither of these medications effectively halts the progression of PF or preserves lung function. As a result, lung transplantation remains the sole viable treatment option for patients in the advanced stages of the disease. Thus, it is imperative to identify new therapeutic agents capable of effectively addressing PF.Methods: Exosomes were harvested from the supernatants of human umbilical cord-derived mesenchymal stem cells (UC-MSCs) transfected with control or miR-486-5p-overexpressing lentivirus using ultracentrifugation and were subsequently resuspended in Minimum Essential Medium (MEM). The immunophenotypes of the exosomes were analyzed via Western blotting, while their concentration was determined using the Nanoparticle Tracking Analysis device, NanoSight NS300. The influence of exosomal microRNA-486-5p (miR-486-5p) derived from UC-MSCs on apoptosis in MRC-5 cells was assessed using flow cytometry, and cell proliferation was evaluated through the CCK8 assay. The expression levels of miR-486-5p, fibroblast growth factor 9 (FGF9), and extracellular matrix (ECM)-related genes were quantified through quantitative reverse transcription-polymerase chain reaction (qRT-PCR).Results: 1)MiR-486-5p inhibits TGF-β1-induced pulmonary fibroblast differentiation by targeting FGF9. 2)Exogenous exosomes facilitated the transfer of miR-486-5p to MRC-5 cells. 3) The presence of exosomal miR-486-5p reduced the mRNA expression of FGF9, fibronectin (Fn), alpha-smooth muscle actin (α-SMA), vimentin, COL1A1, and COL3A1, alongside diminishing FGF9 and vimentin protein expression. 4) In comparison to control exosomes, UC-MSC-derived exosomal miR-486-5p slightly promoted MRC-5 cell apoptosis (P=0.06), but did not significantly impact cell proliferation (P>0.05).Conclusion: Exosomal miR-486-5p derived from UC-MSCs demonstrates potential therapeutic efficacy in regulating fibroblast differentiation by targeting FGF9, thereby mitigating the progression of PF.
Keywords: Pulmonary Fibrosis, Stem Cells, Exosomes, miR-486-5p, Fibroblast differentiation
Received: 09 Dec 2024; Accepted: 09 Jun 2025.
Copyright: © 2025 Shi, Tuo, Liao, Duo and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jie Duo, Qinghai Provincial People's Hospital, Xining, China
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