Details

Autor(en) / Beteiligte

• Yao, Hang
• Qian, Jin
• Bian, Xu-ting
• Guo, Lin
• Tang, Kang-lai
• Tao, Xu

Titel

miR-27b-3p reduces muscle fibrosis during chronic skeletal muscle injury by targeting TGF-[beta]R1/Smad pathway

Ist Teil von

• Journal of orthopaedic surgery and research, 2024-06, Vol.19 (1)

Ort / Verlag

BioMed Central Ltd

Erscheinungsjahr

2024

Link zum Volltext

Quelle

SpringerLink

Beschreibungen/Notizen

• 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-[beta]R1) and the abundance of miR-27b-3p was negatively regulated by TGF-[beta]R1/Smad. Conclusion miR-27b-3p targeting the TGF-[beta]R1/Smad pathway is a novel mechanism for regulating fibrogenic differentiation of FAPs. Increasing abundance of miR-27b-3p, suppressing expression of TGF-[beta]R1 and inhibiting phosphorylation of smad3 presented potential strategies for treating fibrosis in chronic skeletal muscle injury. Keywords: MicroRNAs, Fibro-adipogenic progenitors, Fibrosis, Muscle injury