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The mechanism of TGF-β/miR-155/c-Ski regulates endothelial–mesenchymal transition in human coronary artery endothelial cells

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...

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Autores principales: Wang, Juan, He, Wen, Xu, Xiao, Guo, Liping, Zhang, Yin, Han, Suxia, Shen, Difei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Portland Press Ltd. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569159/
https://www.ncbi.nlm.nih.gov/pubmed/28607031
http://dx.doi.org/10.1042/BSR20160603
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author Wang, Juan
He, Wen
Xu, Xiao
Guo, Liping
Zhang, Yin
Han, Suxia
Shen, Difei
author_facet Wang, Juan
He, Wen
Xu, Xiao
Guo, Liping
Zhang, Yin
Han, Suxia
Shen, Difei
author_sort Wang, Juan
collection PubMed
description 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.
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spelling pubmed-55691592017-09-01 The mechanism of TGF-β/miR-155/c-Ski regulates endothelial–mesenchymal transition in human coronary artery endothelial cells Wang, Juan He, Wen Xu, Xiao Guo, Liping Zhang, Yin Han, Suxia Shen, Difei Biosci Rep Research Articles 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. Portland Press Ltd. 2017-08-24 /pmc/articles/PMC5569159/ /pubmed/28607031 http://dx.doi.org/10.1042/BSR20160603 Text en © 2017 The Author(s). http://creativecommons.org/licenses/by/4.0/This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY) (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Articles
Wang, Juan
He, Wen
Xu, Xiao
Guo, Liping
Zhang, Yin
Han, Suxia
Shen, Difei
The mechanism of TGF-β/miR-155/c-Ski regulates endothelial–mesenchymal transition in human coronary artery endothelial cells
title The mechanism of TGF-β/miR-155/c-Ski regulates endothelial–mesenchymal transition in human coronary artery endothelial cells
title_full The mechanism of TGF-β/miR-155/c-Ski regulates endothelial–mesenchymal transition in human coronary artery endothelial cells
title_fullStr The mechanism of TGF-β/miR-155/c-Ski regulates endothelial–mesenchymal transition in human coronary artery endothelial cells
title_full_unstemmed The mechanism of TGF-β/miR-155/c-Ski regulates endothelial–mesenchymal transition in human coronary artery endothelial cells
title_short The mechanism of TGF-β/miR-155/c-Ski regulates endothelial–mesenchymal transition in human coronary artery endothelial cells
title_sort mechanism of tgf-β/mir-155/c-ski regulates endothelial–mesenchymal transition in human coronary artery endothelial cells
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5569159/
https://www.ncbi.nlm.nih.gov/pubmed/28607031
http://dx.doi.org/10.1042/BSR20160603
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