The mechanism of TGF-β/miR-155/c-Ski regulates endothelial–mesenchymal transition in human coronary artery endothelial cells. Issue 4 (24th August 2017)

• Record Type: Journal Article
• Authors: Wang, Juan; He, Wen; Xu, Xiao; Guo, Liping; Zhang, Yin; Han, Suxia; Shen, Difei
• Is Part Of: Bioscience reports. Volume 37:Issue 4(2017)
• Publication Date: 2017-08-24
• Subjects: cardiac fibrosis -- c-Ski -- endothelial-mesenchymal transition (EndMT) -- Human coronary artery endothelial cells (HCAECs) -- miR-155 -- transforming growth factor-β (TGF-β); Molecular biology -- Periodicals; Cytology -- Periodicals; 572.8
• DOI: 10.1042/BSR20160603
• Languages: English
• ISSNs: 0144-8463

Abstract

Abstract : Human coronary artery endothelial cells (HCAECs) have the potential to undergo fibrogenic endothelial–mesenchymal transition (EndMT), which results in matrix-producing fibroblasts and thereby contributes to the pathogenesis of cardiac fibrosis. Recently, the profibrotic cytokine transforming growth factor-β (TGF-β) is shown to be the crucial pathogenic driver which has been verified to induce EndMT. C-Ski is an important regulator of TGF-β signaling. However, the detailed role of c-Ski and the molecular mechanisms by which c-Ski affects TGF-β-induced EndMT in HCAECs are not largely elucidated. In the present study, we treated HCAECs with TGF-β of different concentrations to induce EndMT. We found that overexpression of c-Ski in HCAECs either blocked EndMT via hindering Vimentin, Snail, Slug, and Twist expression while enhancing CD31 expression, with or without TGF-β treatment. In contrast, suppression of c-Ski further enhanced EndMT. Currently, miRNA expression disorder has been frequently reported associating with cardiac fibrosis. By using online tools, we regarded miR-155 as a candidate miRNA that could target c-Ski, which was verified using luciferase assays. C-Ski expression was negatively regulated by miR-155. TGF-β-induced EndMT was inhibited by miR-155 silence; the effect of TGF-β on Vimentin, CD31, Snail, Slug, and Twist could be partially restored by miR-155. Altogether, these findings will shed light on the role and mechanism by which miR-155 regulates TGF-β-induced HCAECs EndMT via c-Ski to affect cardiac fibrosis, and miR-155/c-Ski may represent novel biomarkers and therapeutic targets in the treatment of cardiac fibrosis.