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- Title
miR-27b-3p reduces muscle fibrosis during chronic skeletal muscle injury by targeting TGF-βR1/Smad pathway.
- Authors
Yao, Hang; Qian, Jin; Bian, Xu-ting; Guo, Lin; Tang, Kang-lai; Tao, Xu
- Abstract
Background: Fibrosis is a significant pathological feature of chronic skeletal muscle injury, profoundly affecting muscle regeneration. Fibro-adipogenic progenitors (FAPs) have the ability to differentiate into myofibroblasts, acting as a primary source of extracellular matrix (ECM). the process by which FAPs differentiate into myofibroblasts during chronic skeletal muscle injury remains inadequately explored. Method: mouse model with sciatic nerve denervated was constructed and miRNA expression profiles between the mouse model and uninjured mouse were analyzed. qRT/PCR and immunofluorescence elucidated the effect of miR-27b-3p on fibrosis in vivo and in vitro. Dual-luciferase reporter identified the target gene of miR-27b-3p, and finally knocked down or overexpressed the target gene and phosphorylation inhibition of Smad verified the influence of downstream molecules on the abundance of miR-27b-3p and fibrogenic differentiation of FAPs. Result: FAPs derived from a mouse model with sciatic nerves denervated exhibited a progressively worsening fibrotic phenotype over time. Introducing agomiR-27b-3p effectively suppressed fibrosis both in vitro and in vivo. MiR-27b-3p targeted Transforming Growth Factor Beta Receptor 1 (TGF-βR1) and the abundance of miR-27b-3p was negatively regulated by TGF-βR1/Smad. Conclusion: miR-27b-3p targeting the TGF-βR1/Smad pathway is a novel mechanism for regulating fibrogenic differentiation of FAPs. Increasing abundance of miR-27b-3p, suppressing expression of TGF-βR1 and inhibiting phosphorylation of smad3 presented potential strategies for treating fibrosis in chronic skeletal muscle injury.
- Subjects
SKELETAL muscle injuries; GENE therapy; BIOLOGICAL models; IN vitro studies; CARRIER proteins; PHOSPHORYLATION; SCIATIC nerve; RESEARCH funding; MUSCLE proteins; MICRORNA; CELLULAR signal transduction; REVERSE transcriptase polymerase chain reaction; FLUORESCENT antibody technique; IN vivo studies; FIBROSIS; GENE expression; MICE; ANIMAL experimentation; GENE expression profiling; DENERVATION; CELL differentiation; STEM cells; TRANSFORMING growth factors-beta
- Publication
Journal of Orthopaedic Surgery & Research, 2024, Vol 19, Issue 1, p1
- ISSN
1749-799X
- Publication type
Article
- DOI
10.1186/s13018-024-04733-9