Myostatin induces tumor necrosis factor-α expression in rheumatoid arthritis synovial fibroblasts through the PI3K-Akt signaling pathway
Myostatin induces tumor necrosis factor-α expression in rheumatoid arthritis synovial fibroblasts through the PI3K-Akt signaling pathway
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肌生长抑制素通过 PI3K-Akt 信号通路诱导类风湿性关节炎滑膜成纤维细胞中肿瘤坏死因子-α 的表达。
DOI：
10.1002/jcp.27665
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发表时间：
2019-06-01
影响因子：
5.6
通讯作者：
Tang, Chih-Hsin
中科院分区：
文献类型：
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作者：
Su, Chen-Ming;Hu, Sung-Lin;Tang, Chih-Hsin
在类风湿性关节炎（RA）（一种慢性炎症性疾病）中，肌肉质量的丧失是导致RA患者肌肉力量丧失的重要因素。肌生长抑制素是一种参与肌肉肥大和肌生成过程的肌细胞因子，可促进破骨细胞分化和炎症反应。在这里，我们研究了肌生长抑制素在RA滑膜炎症中的作用机制。我们发现RA滑膜组织中肌生长抑制素和肿瘤坏死因子-α（TNF-α）（一种众所周知的促炎细胞因子）之间呈正相关。我们的体外研究结果还表明，肌肉生长抑制素通过磷脂酰肌醇3-激酶（PI 3 K）-Akt-AP-1信号通路剂量依赖性地诱导TNF-α表达。肌肉生长抑制素处理人MH 7A细胞刺激AP-1诱导的荧光素酶活性和TNF-α启动子上c-Jun结合位点的激活。我们的研究结果表明，肌肉生长抑制素通过PI 3 K-Akt-AP-1信号通路增加人RA滑膜成纤维细胞中TNF-α的表达。肌生长抑制素似乎是RA治疗的一个有希望的靶点。
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-alpha (TNF-alpha), a well-known proinflammatory cytokine, in RA synovial tissue. Our in vitro results also showed that myostatin dose-dependently induced TNF-alpha 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-alpha promoter. Our results indicated that myostatin increases TNF-alpha expression via the PI3K-Akt-AP-1 signaling pathway in human RA synovial fibroblasts. Myostatin appears to be a promising target in RA therapy.