Back to Search
Start Over
Myostatin induces tumor necrosis factor‐α expression in rheumatoid arthritis synovial fibroblasts through the PI3K–Akt signaling pathway
- Source :
- Journal of Cellular Physiology. 234:9793-9801
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- In rheumatoid arthritis (RA), a chronic inflammatory disease, loss of muscle mass is an important contributor to the loss of muscle strength in RA patients. Myostatin, a myokine involved in the process of muscle hypertrophy and myogenesis, enhances osteoclast differentiation and inflammation. Here, we investigated the mechanisms of myostatin in RA synovial inflammation. We found a positive correlation between myostatin and tumor necrosis factor-α (TNF-α), a well-known proinflammatory cytokine, in RA synovial tissue. Our in vitro results also showed that myostatin dose-dependently induced TNF-α expression through the phosphatidylinositol 3-kinase (PI3K)-Akt-AP-1 signaling pathway. Myostatin treatment of human MH7A cells stimulated AP-1-induced luciferase activity and activation of the c-Jun binding site on the TNF-α promoter. Our results indicated that myostatin increases TNF-α expression via the PI3K-Akt-AP-1 signaling pathway in human RA synovial fibroblasts. Myostatin appears to be a promising target in RA therapy.
- Subjects :
- 0301 basic medicine
Physiology
Clinical Biochemistry
Inflammation
Myostatin
Cell Line
Proinflammatory cytokine
Arthritis, Rheumatoid
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Myokine
medicine
Humans
PI3K/AKT/mTOR pathway
biology
Tumor Necrosis Factor-alpha
Chemistry
Myogenesis
Synovial Membrane
Cell Biology
Fibroblasts
musculoskeletal system
Transcription Factor AP-1
030104 developmental biology
Gene Expression Regulation
030220 oncology & carcinogenesis
Cancer research
biology.protein
Tumor necrosis factor alpha
medicine.symptom
Signal transduction
Proto-Oncogene Proteins c-akt
Signal Transduction
Subjects
Details
- ISSN :
- 10974652 and 00219541
- Volume :
- 234
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Physiology
- Accession number :
- edsair.doi.dedup.....37e3c0e5a0f55d10f8d4d962f2f88635