Serelaxin inhibits differentiation and fibrotic behaviors of cardiac fibroblasts by suppressing ALK-5/Smad2/3 signaling pathway

Journal Article · Mon Jan 15 04:00:00 EST 2018 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2017.10.004· OSTI ID:23082541

Wu, Xue-ping; Wang, Hai-jie; Wang, Yong-li; Shen, Hao-ran; Tan, Yu-zhen ^[1]

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1. Department of Anatomy, Histology and Embryology, Shanghai Medical School of Fudan University, 277 138 Yixueyuan Road, Shanghai, 200032 (China)

Highlights: • Serelaxin inhibits differentiation of cardiac fibroblasts towards myofibroblasts. • Serelaxin suppresses ALK-5/Smad2/3 signaling pathway. • Serelaxin up-regulates MMP-2/TIMP-2 ratio and IL-10 secretion. Serelaxin, a recombinant form of human relaxin-2, is currently regarded as a novel drug for treatment of acute heart failure. However, whether therapeutic effects of serelaxin are achieved by inhibiting cardiac fibrosis remains unclear. In this study, we investigate effects of serelaxin on inhibiting cardiac fibrosis. Cardiac fibroblasts (CFs) were isolated from the hearts of adult rats. Effects of serelaxin on differentiation of CFs towards myofibroblasts (MFs) and their fibrotic behaviors after induction with TGF-β1 were examined. Synthesis and degradation of collagens, secretion of IL-10, and expression of ALK-5 and p-Smad2/3 of TGF-β1-induced cells were assessed after treatment with serelaxin. Serelaxin inhibited differentiation of TGF-β1-induced CFs towards MFs, and reduced proliferation and migration of the induced cells. Moreover, serelaxin down-regulated expression of collagen I/III and TIMP-2, and up-regulated expression of MMP-2 and MMP-9 in the cells. After treatment with serelaxin, activity of MMP-2 and MMP-9 and secretion of IL-10 increased, expression of ALK-5 and the level of Smad2/3 phosphorylation was reduced significantly. These results suggest that serelaxin can inhibit differentiation of TGF-β1-induced CFs towards MFs, reduce production of collagens by suppressing ALK-5/Smad2/3 signaling pathway, and enhance extracellular matrix degradation by increasing MMP-2/TIMP-2 ratio and IL-10 secretion. Serelaxin may be a potential therapeutic drug for inhibiting cardiac fibrosis.

• OSTI ID: 23082541
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 362; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
COLLAGEN
FIBROBLASTS
FIBROSIS
HEART FAILURE
RATS