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MiR-1290 promotes myoblast differentiation and protects against myotube atrophy via Akt/p70/FoxO3 pathway regulation
- Source :
- Skeletal Muscle, Skeletal Muscle, Vol 11, Iss 1, Pp 1-12 (2021)
- Publication Year :
- 2020
-
Abstract
- Background Sarcopenia is a common skeletal disease related to myogenic disorders and muscle atrophy. Current clinical management has limited effectiveness. We sought to investigate the role of miR-1290 in myoblast differentiation and muscle atrophy. Methods By transfecting miR-1290 into C2C12 cells, we investigated whether miR-1290 regulates myogenesis and myotube atrophy via AKT/P70 signaling pathway. MHC staining was performed to assess myoblast differentiation. Differentiation-related MHC, Myod, and Myog protein levels, and atrophy-related MuRF1 and atrogin-1 were explored by western blot. An LPS-induced muscle atrophy rat model was developed. RT-PCR was conducted to analyze miR-1290 serum levels in muscle atrophy patients and normal controls (NCs). Results The miR-1290 transfection increased MHC-positive cells and MHC, Myod, and Myog protein levels in the miR-1290 transfection group, demonstrating that miR-1290 promoted C2C12 myoblast differentiation. Myotube diameter in the miR-1290 transfection group was higher than in the TNF-α-induced model group. Western blot analysis showed decreased MuRF1 and atrogin-1 levels in the miR-1290 transfection group compared with the model group, demonstrating that miR-1290 protected against myoblast cellular atrophy. Luciferase assay and western blot analysis showed that miR-1290 regulation was likely caused by AKT/p70/FOXO3 phosphorylation activation. In the LPS-induced muscle atrophy rat model, miR-1290 mimics ameliorated gastrocnemius muscle loss and increased muscle fiber cross-sectional area. Clinically, miR-1290 serum level was significantly decreased in muscle atrophy patients. Conclusions We found that miR-1290 enhances myoblast differentiation and inhibits myotube atrophy through Akt/p70/FoxO3 signaling in vitro and in vivo. In addition, miR-1290 may be a potential therapeutic target for sarcopenia treatment.
- Subjects :
- 0301 basic medicine
lcsh:Diseases of the musculoskeletal system
Muscle Fibers, Skeletal
miR-1290
P70-S6 Kinase 1
Biology
MyoD
Cell Line
Myoblasts
03 medical and health sciences
0302 clinical medicine
Atrophy
medicine
Myocyte
Animals
Humans
Orthopedics and Sports Medicine
Molecular Biology
Protein kinase B
Myogenesis
Research
Forkhead Box Protein O3
Cell Differentiation
Cell Biology
medicine.disease
musculoskeletal system
Muscle atrophy
Cell biology
Rats
Akt/P70/FoxO3
MicroRNAs
Muscular Atrophy
030104 developmental biology
Myoblast differentiation
030220 oncology & carcinogenesis
lcsh:RC925-935
medicine.symptom
C2C12
Proto-Oncogene Proteins c-akt
Subjects
Details
- ISSN :
- 20445040
- Volume :
- 11
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Skeletal muscle
- Accession number :
- edsair.doi.dedup.....88ac9cfeca03461b3643a9189bbb7efd