ヒグチ　トモアキ   Higuchi Tomoaki   樋口　智昭    所属   医学部 医学科（東京女子医科大学病院）    職種   寄附部門講師
論文種別	原著
言語種別	英語
査読の有無	査読なし
表題	Sildenafil attenuates the fibrotic phenotype of skin fibroblasts in patients with systemic sclerosis.
掲載誌名	正式名：Clinical immunology (Orlando, Fla.) 略　 称：Clin Immunol ISSNコード：(1521-7035)1521-6616(Linking)
掲載区分	国外
巻・号・頁	161(2),pp.333-8
著者・共著者	Higuchi Tomoaki†, Kawaguchi Yasushi*, Takagi Kae, Tochimoto Akiko, Ota Yuko, Katsumata Yasuhiro, Ichida Hisae, Hanaoka Masanori, Kawasumi Hidenaga, Tochihara Mari, Yamanaka Hisashi
担当区分	筆頭著者
発行年月	2015/12
概要	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