期刊
CLINICAL IMMUNOLOGY
卷 161, 期 2, 页码 333-338出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2015.09.010
关键词
Sildenafil; Systemic sclerosis; Fibrosis; CGMP
类别
资金
- Ministry of Health, Labour and Welfare, Japan
Systemic sclerosis (SSc) is a multi-organ fibrotic disease that affects the skin and various internal organs. Therapeutic strategies for tissue fibrosis have not been established; however, aberrantly activated fibroblasts in affected lesions are key targets for modulating fibrosis. Recently, increased intracellular cyclic GMP (cGMP) levels were demonstrated to improve fibrosis levels in various diseases. The purpose of this study was to assess the antifibrotic properties of cGMP in cultured fibroblasts from patients with SSc. The phosphodiesterase (PDE) 5 inhibitor sildenafil increased the intracellular cGMP levels in skin fibroblasts in a dose-dependent manner. Sildenafil treatment also significantly decreased the expression of several pro-fibrotic factors that were upregulated by TGF-beta 1 treatment in SSc skin fibroblasts. These inhibitory effects occurred via non-canonical TGF-beta signaling. Our findings revealed that sildenafil might be a novel strategy to treat tissue fibrosis and vasculopathy in SSc. (C) 2015 Elsevier Inc. All rights reserved.
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