miR-491-5p inhibits Emilin 1 to promote fibroblasts proliferation and fibrosis in gluteal muscle contracture via TGF-Beta1/Smad2 pathway
Language English Country Czech Republic Media print-electronic
Document type Journal Article
PubMed
35275699
PubMed Central
PMC9150558
DOI
10.33549/physiolres.934804
PII: 934804
Knihovny.cz E-resources
- MeSH
- Fibroblasts metabolism MeSH
- Fibrosis MeSH
- Contracture * pathology MeSH
- Muscle, Skeletal metabolism MeSH
- Humans MeSH
- Membrane Glycoproteins MeSH
- RNA, Messenger metabolism MeSH
- MicroRNAs * genetics metabolism MeSH
- Cell Proliferation MeSH
- Smad2 Protein metabolism MeSH
- Transforming Growth Factor beta1 genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- elastin microfibril interface located protein MeSH Browser
- Membrane Glycoproteins MeSH
- RNA, Messenger MeSH
- MicroRNAs * MeSH
- MIRN491 microRNA, human MeSH Browser
- Smad2 Protein MeSH
- SMAD2 protein, human MeSH Browser
- Transforming Growth Factor beta1 MeSH
Gluteal muscle contracture (GMC) is a chronic fibrotic disease of gluteal muscles due to multiple etiologies. Emilin 1 plays a determinant role in fibers formation, but its role in the progression of GMC remains unclear. The present study was aimed to search for the predictive role and regulatory mechanism of Emilin 1 on GMC. Here, Protein and mRNA expression of Emilin 1 were decreased in GMC tissues compared to normal muscle tissues. Using the anslysis of target prediction, Emilin 1 was observed to be a potential downstream sponge of miR-491-5p. In comparison to Emilin 1, miR-491-5p showed a aberrant elevation in GMC tissues, which was further proven to have a negative correlation with Emilin 1. The direct binding of miR-491-5p to Emilin 1 mRNA was confirmed by luciferase reporter gene assay, and miR-491-5p mimics inhibited, while miR-491-5p inhibitor promoted the protein expression and secretion of Emilin 1 in contraction bands (CB) fibroblasts. Additionally, miR-491-5p mimics promoted the expression of cyclin-dependent kinase 2 and cyclin D1 and the proliferation of CB fibroblasts, which could be reversed by Emilin 1 overexpression. Mechanistically, miR-491-5p mimics possibly activated transforming growth factor beta1 (TGF-beta1)/Smad3 signal cascade via binding to 3'-untranslated region of Emilin 1 mRNA, thereby promoting the progression of fibrosis of CB fibroblasts. Collectively, miR-491-5p inhibited Emilin 1 expression, and subsequently promoted CB fibroblasts proliferation and fibrosis via activating TGF-beta1/Smad3 signal axis. MiR-491-5p might be a potentially effective biomarker for predicting GMC, providing a novel therapeutic strategy for GMC.
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