Open Access

ARTICLE

Role of endothelin-1 in the skin fibrosis of systemic sclerosis

J. Jing, T. T. Dou, J. Q. Yang, X. B. Chen, H. L. Cao, M. Min, S. Q. Cai, M. Zheng, X. Y. Man

Department of Dermatology, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

* Corresponding Authors: Xiao-Yong, ;

European Cytokine Network 2015, 26(1), 10-14. https://doi.org/10.1684/ecn.2015.0360

Abstract

Endothelin-1 (ET-1) acts as a key regulator of vasoconstriction and fibrosis. Many previous studies have focused on the role of ET-1 in scleroderma (systemic sclerosis, SSc). We investigated the effects of ET-1 on the production of extracellular matrix in SSc and normal skin fibroblasts. Primary cultured dermal fibroblasts from SSc patients and healthy controls were treated with ET-1 (25 ng/mL) for 0 min, 15 min, 1 h, 24 h, 48 h and 72 h, respectively. Our results showed that, in SSc fibroblasts, ET-1 upregulated collagen type I, connective tissue growth factor (CTGF), type I plasminogen activator inhibitor (PAI-1) and pAkt in a time-dependent manner within 72 h; in normal fibroblasts, 25 ng/mL ET-1 stimulation correlated with high levels of CTGF, PAI-1 and pAkt. The secretion of fibronectin (FN), collagen type I, and PAI-1 is markedly increased in the supernatant of both SSc fibroblasts and normal fibroblasts. Furthermore, ET-1 phosphorylates Smad2 and Smad3 in normal fibroblasts, but not in SSc fibroblasts. In conclusion, our results demonstrated that ET-1 may induce fibrosis in dermal fibroblasts through Akt signals.

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