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miR-27b-3p reduces muscle fibrosis during chronic skeletal muscle injury by targeting TGF-βR1/Smad pathway.
- Source :
-
Journal of Orthopaedic Surgery & Research . 6/2/2024, Vol. 19 Issue 1, p1-14. 14p. - Publication Year :
- 2024
-
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. [ABSTRACT FROM AUTHOR]
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1749799X
- Volume :
- 19
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Orthopaedic Surgery & Research
- Publication Type :
- Academic Journal
- Accession number :
- 177597905
- Full Text :
- https://doi.org/10.1186/s13018-024-04733-9