期刊
EXPERIMENTAL DERMATOLOGY
卷 26, 期 11, 页码 1139-1143出版社
WILEY
DOI: 10.1111/exd.13366
关键词
fibrosis; scleroderma
类别
资金
- Grant for Scientific Research from Japanese Ministry of Education, Science, Sports and Culture
- project research on intractable diseases from Japanese Ministry of Health, Labor and Welfare
- Grants-in-Aid for Scientific Research [16K10165, 15K09772] Funding Source: KAKEN
Inhibition of transforming growth factor (TGF)-beta 1 signalling may be one of the most reliable approaches to treat skin fibrosis of scleroderma. Although there have been many basic researches of TGF- blockade reagents, few of them were proved to have inhibitory effects on fibrosis both in vitro and in vivo. In this study, we randomly chose four commercially available low molecular weightcompounds(Repsox, LY2109761, LY364947 and K02288) from TGF-1 inhibitor library, and compared their antifibrotic effects in vitro and in vivo. We demonstrated that Repsox has the most potent inhibitory effects on TGF--induced expression of CTGF and collagen of cultured normal dermal fibroblasts in vitro and their constitutive overexpression of scleroderma fibroblast in vitro. In addition, Repsox could attenuate skin fibrosis by bleomycin in vivo, via the downregulation of CTGF or collagen. Our results may facilitate clinical trial of Repsox against fibrotic diseases in future.
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