The Role of c‐SKI in Regulation of TGFβ‐Induced Human Cardiac Fibroblast Proliferation and ECM Protein Expression. Issue 7 (27th March 2017)

• Record Type: Journal Article
• Authors: Wang, Juan; Guo, Liping; Shen, Difei; Xu, Xiao; Wang, Jiaping; Han, Suxia; He, Wen
• Is Part Of: Journal of cellular biochemistry. Volume 118:Issue 7(2017)
• Page Start: 1911
• Page End: 1920
• Publication Date: 2017-03-27
• Subjects: CARDIAC FIBROSIS -- EXTRACELLULAR MATRIX (ECM) -- TRANSFORMING GROWTH FACTOR β 1 (TGFβ1) -- miR‐155 -- miR‐17 -- c‐Ski; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.25935
• Languages: English
• ISSNs: 0730-2312

Abstract

ABSTRACT: 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 β 1 (TGFβ1) is as an essential inducing factor of cardiac fibrosis. C‐Ski protein has been identified as an inhibitory regulator of TGFβ signaling. In the present study, we revealed the repressive effect of c‐Ski on TGFβ1‐induced human cardiac fibroblast (HCFB) proliferation and ECM protein increase (Collagen I and α‐SMA). Moreover, miR‐155 and miR‐17 could inhibit SKI mRNA expression by direct binding to the 3′UTR of SKI, so as to reduce c‐Ski protein level. Either miR‐155 inhibition or miR‐17 inhibition could reverse TGFβ1‐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 TGFβ1 signaling. J. Cell. Biochem. 118: 1911–1920, 2017. © 2017 Wiley Periodicals, Inc. Abstract : We revealed that c‐Ski could repress, while miR‐155/miR‐17 could inhibit TGFβ1‐induced cardiac fibroblast proliferation and ECM protein increase. The present study provided a potential therapy to treat cardiac fibrosis by inhibiting miR‐155/miR‐17 so as to restore the effect of c‐Ski on suppressing TGFβ1 signaling.