The Role of c-SKI in Regulation of TGF beta-Induced Human Cardiac Fibroblast Proliferation and ECM Protein Expression

作者：Wang, Juan; Guo, Liping; Shen, Difei; Xu, Xiao; Wang, Jiaping; Han, Suxia^*; He, Wen^*

来源：Journal of Cellular Biochemistry, 2017, 118(7): 1911-1920.

DOI：10.1002/jcb.25935

• CARDIAC FIBROSIS
• EXTRACELLULAR MATRIX (ECM)
• TRANSFORMING GROWTH FACTOR beta 1 (TGF beta 1)
• miR-155
• miR-17
• c-Ski

Cardiac fibrosis is characterized by over-deposition of extracellular matrix (ECM) proteins and over-proliferation of cardiac fibroblast, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. Transforming growth factor beta 1 (TGF beta 1) is as an essential inducing factor of cardiac fibrosis. C-Ski protein has been identified as an inhibitory regulator of TGF beta signaling. In the present study, we revealed the repressive effect of c-Ski on TGF beta 1-induced human cardiac fibroblast (HCFB) proliferation and ECM protein increase (Collagen I and alpha-SMA). Moreover, miR-155 and miR-17 could inhibit SKI mRNA expression by direct binding to the 30UTR of SKI, so as to reduce c-Ski protein level. Either miR-155 inhibition or miR-17 inhibition could reverse TGF beta 1-induced HCFB proliferation and ECM protein increase. Taken together, we provided a potential therapy to treat cardiac fibrosis by inhibiting miR-155/miR-17 so as to restore the repressive effect of c-Ski on TGF beta 1 signaling.

• 出版日期2017-7
• 单位武汉大学; 新疆医科大学