強皮症モデルマウスの皮膚に発現した線維化・α-SMAに対する外用セレコキシブの効果の検討

• Published in: 日本薬理学会年会要旨集 p. 1-P-061
• Main Authors: 豊平, 由美子, 松永, 洋明, 幾島, 栄悟, 石兼, 真, 瀧口, 知浩, 岸上, 赳大, 高橋, 富美
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: fibroblast; skin; transforming growth factor
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_1-P-061

Systemic sclerosis (SSc) is a connective tissue disorder characterized by the development of skin fibrosis. No topical treatment for the skin manifestations of SSc has been developed. We previously reported that celecoxib, a selective inhibitor of COX-2, and/or its derivative DM-celecoxib suppressed cardiac and renal fibrosis. Therefore, the effect of celecoxib on the SSc fibrosis was investigated. In in-vivo study, bleomycin was injected s.c. into a single location of the hair less mouse Hos:HR1 every 3 days for 10 days to induce scleroderma. For the treatment of celecoxib, celecoxib was dissolved into acetone and topically applied, whereas control mice received acetone only. Ten days after the first injection, skin section was obtained and histological analysis were performed. To clarify the mechanism of celecoxib action, normal human skin fibroblast cell line NB1RGB was stimulated with TGF-β to induced fibroblast-myofibroblast transformation and the effects of celecoxib on the expression of α-SMA was analyzed. We found that topical application of celecoxib significantly decreased skin thickness and the expression of α-SMA in bleomycin-induced scleroderma model mice. Consistent with these results, celecoxib inhibited the expression of α-SMA induced by TGF-β in NB1RGB cells. Further studies are now conducting to clarify the action of celecoxib.