title: The Role of c-SKI in Regulation of TGFβ-Induced Human Cardiac Fibroblast Proliferation and ECM Protein Expression.
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.
authors.affiliation: Department of Cardiology, the Fifth Affiliated Hospital of Xin Jiang Medical University, Urumchi, 830001,, Xin Jiang, China.
authors.forename: Juan
authors.identifier: 0000-0003-4592-4613
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, the Fifth Affiliated Hospital of Xin Jiang Medical University, Urumchi, 830001,, Xin Jiang, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, China.
authors.forename: Difei
authors.initials: D
authors.lastname: Shen
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Xin Jiang Medical University, Urumchi, 830001,, Xin Jiang, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, the Fifth Affiliated Hospital of Xin Jiang Medical University, Urumchi, 830001,, Xin Jiang, China.
authors.forename: Jiaping
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Cardiology, the Fifth Affiliated Hospital of Xin Jiang Medical University, Urumchi, 830001,, Xin Jiang, China.
authors.forename: Suxia
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Pharmacy, the Fifth Affiliated Hospital of Xin Jiang Medical University, Urumchi, 830001,, Xin Jiang, China.
authors.forename: Wen
authors.initials: W
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
chemical_list: D020413:3' Untranslated Regions; D004268:DNA-Binding Proteins; D016326:Extracellular Matrix Proteins; C524942:MIRN155 microRNA, human; C524941:MIRN17 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; C060614:SKI protein, human
keywords: CARDIAC FIBROSIS; EXTRACELLULAR MATRIX (ECM); TRANSFORMING GROWTH FACTOR β 1 (TGFβ1); c-Ski; miR-155; miR-17