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樋口 智昭
Department School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine Position Endowed Assistant Professor |
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| Article types | Original article |
| Language | English |
| Peer review | Non peer reviewed |
| Title | Sildenafil attenuates the fibrotic phenotype of skin fibroblasts in patients with systemic sclerosis. |
| Journal | Formal name：Clinical immunology (Orlando, Fla.) Abbreviation：Clin Immunol ISSN code：(1521-7035)1521-6616(Linking) |
| Domestic / Foregin | Foregin |
| Volume, Issue, Page | 161(2),pp.333-8 |
| Author and coauthor | Higuchi Tomoaki†, Kawaguchi Yasushi*, Takagi Kae, Tochimoto Akiko, Ota Yuko, Katsumata Yasuhiro, Ichida Hisae, Hanaoka Masanori, Kawasumi Hidenaga, Tochihara Mari, Yamanaka Hisashi |
| Authorship | Lead author |
| Publication date | 2015/12 |
| Summary | 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 anti-fibrotic 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-β1 treatment in SSc skin fibroblasts. These inhibitory effects occurred via non-canonical TGF-β signaling. Our findings revealed that sildenafil might be a novel strategy to treat tissue fibrosis and vasculopathy in SSc. |
| DOI | 10.1016/j.clim.2015.09.010 |
| PMID | 26387628 |