Back to Journals » Drug Design, Development and Therapy » Volume 9

Relaxin inhibits cardiac fibrosis and endothelial–mesenchymal transition via the Notch pathway

Authors Zhou X, Chen X, Cai JJ, Chen LZ, Gong YS, Wang LX, Gao Z, Zhang HQ, Huang WJ, Zhou H

Received 25 March 2015

Accepted for publication 26 May 2015

Published 11 August 2015 Volume 2015:9 Pages 4599—4611


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 5

Editor who approved publication: Professor Shu-Feng Zhou

X Zhou,1 X Chen,2 JJ Cai,2 LZ Chen,3 YS Gong,4 LX Wang,5 Z Gao,1 HQ Zhang,1 WJ Huang,1 H Zhou1

1Department of Cardiology, The First Affiliated Hospital of Wenzhou Medical University, 2Wenzhou Medical University, 3Department of Clinical Laboratory, Wenzhou Central Hospital, 4Institute of Hypoxia Medicine, Wenzhou Medical University, 5Department of Respiratory Medicine, Wenzhou Medical University, Wenzhou, People’s Republic of China

Background: Relaxin (RLX) can prevent cardiac fibrosis. We aimed to investigate the possible mechanism and signal transduction pathway of RLX inhibiting cardiac fibrosis.
Methods: Isoproterenol (5 mg·kg-1·d-1) was used to establish the cardiac fibrosis model in rats, which were administered RLX. The cardiac function, related targets of cardiac fibrosis, and endothelial–mesenchymal transition (EndMT) were measured. Transforming growth factor β (TGF-β) was used to induce EndMT in human umbilical vein endothelial cells, which were pretreated with RLX, 200 ng·mL-1, then with the inhibitor of Notch. Transwell cell migration was used to evaluate cell migration. CD31 and vimentin content was determined by immunofluorescence staining and Western blot analysis. Notch protein level was examined by Western blot analysis.
Results: RLX improved cardiac function in rats with cardiac fibrosis; it reduced the content of collagen I and III, increased the microvascular density of the myocardium, and suppressed the EndMT in heart tissue. In vitro, RLX decreased the mobility of human umbilical vein endothelial cells induced by TGF-β, increased the expression of endothelial CD31, and decreased vimentin content. Compared to TGF-β and RLX co-culture alone, TGF-β + RLX + Notch inhibitor increased cell mobility and the EndMT, but decreased the levels of Notch-1, HES-1, and Jagged-1 proteins.
Conclusion: RLX may inhibit the cardiac fibrosis via EndMT by Notch-mediated signaling.

Keywords: relaxin, endothelial to mesenchymal transition, transforming growth factor β, myocardial fibrosis, Notch

Corrigendum for this paper has been published.

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]