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The Role of c‐SKI in Regulation of TGFβ‐Induced Human Cardiac Fibroblast Proliferation and ECM Protein Expression
Author(s) -
Wang Juan,
Guo Liping,
Shen Difei,
Xu Xiao,
Wang Jiaping,
Han Suxia,
He Wen
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25935
Subject(s) - cardiac fibrosis , transforming growth factor , extracellular matrix , fibroblast , microbiology and biotechnology , fibrosis , signal transduction , regulator , chemistry , cell growth , biology , cancer research , medicine , biochemistry , gene , in vitro
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.