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

Oct 9, 2017Experimental cell research

Serelaxin may reduce scarring by blocking a key signaling pathway in heart support cells

AI simplified

Longevity & Aging on OpenScience ↗PubMed ↗DOI ↗

Abstract

Serelaxin inhibited the differentiation of cardiac fibroblasts into myofibroblasts by reducing key signaling pathways.

Serelaxin reduced proliferation and migration of TGF-β1-induced cardiac fibroblasts.
The treatment down-regulated collagen I/III and TIMP-2 expression while up-regulating MMP-2 and MMP-9 expression.
After serelaxin treatment, activity of MMP-2 and MMP-9 increased, and IL-10 secretion was enhanced.
Expression of ALK-5 and levels of phosphorylated Smad2/3 were significantly reduced following serelaxin treatment.
These findings suggest that serelaxin may inhibit cardiac fibrosis by modulating fibroblast behavior and extracellular matrix dynamics.

AI simplified

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.

Full Text

Full text is available at the source.

View full text (XML) ↗View full text ↗

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

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief

Abstract

Full Text

Related papers

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the longevity & aging brief