FGF6 enhances muscle regeneration after nerve injury by relying on ERK1/2 mechanism

Autor: Biao Cheng, Cai Qiuchen, Heng’an Ge, Wu Peng, Min Zhu, Sudan Xu, Qing'’gang Zhang, Chao Xue, Genbin Wu
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Fibroblast Growth Factor 6
Primary Cell Culture
MyoD
030226 pharmacology & pharmacy
General Biochemistry
Genetics and Molecular Biology
Cell Line
Myoblasts
Rats
Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
Cell Movement
Peripheral Nerve Injuries
medicine
Myocyte
Animals
Regeneration
Cyclin D1
Receptor
Fibroblast Growth Factor
Type 4
Receptor
Fibroblast Growth Factor
Type 1
General Pharmacology
Toxicology and Pharmaceutics
RNA
Small Interfering
Muscle
Skeletal
Myogenin
Cell Proliferation
MyoD Protein
Denervation
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Myosin Heavy Chains
Chemistry
Skeletal muscle
Cell Differentiation
General Medicine
Nerve injury
musculoskeletal system
Sciatic Nerve
Muscle Denervation
Cell biology
Rats
030104 developmental biology
medicine.anatomical_structure
Gene Expression Regulation
Peripheral nerve injury
medicine.symptom
tissues
C2C12
Zdroj: Life sciences. 248
ISSN: 1879-0631
Popis: Background Severe peripheral nerve injury leads to skeletal muscle atrophy and impaired limb function that is not sufficiently improved by existing treatments. Fibroblast growth factor 6 (FGF6) is involved in tissue regeneration and is dysregulated in denervated rat muscles. However, the way that FGF6 affects skeletal muscle repair after peripheral nerve injury has not been fully elucidated. Methods In this study, we investigated the role of FGF6 in the regeneration of denervated muscles using myoblast cells and an in vivo model of peripheral nerve injury. Results FGF6 promoted the viability and migration of C2C12 and primary myoblasts in a dose-dependent manner through FGFR1-mediated upregulation of cyclin D1. Low concentrations of FGF6 promoted myoblast differentiation through FGFR4-mediated activation of ERK1/2, which upregulated expression of MyHC, MyoD, and myogenin. FGFR-1, FGFR4, MyoD, and myogenin were not upregulated when FGF6 expression was inhibited in myoblasts by shRNA-mediated knockdown. Injection of FGF6 into denervated rat muscles enhanced the MyHC-IIb muscle fiber phenotype and prevented muscular atrophy. Conclusion These findings indicate that FGF6 reduces skeletal muscle atrophy by relying on the ERK1/2 mechanism and enhances the conversion of slow muscle to fast muscle fibers, thereby promoting functional recovery of regenerated skeletal muscle after innervation.
Databáze: OpenAIRE
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