2-B-P-049 〇有岡 将基、石兼 真、高橋 富美 Masaki Arioka, Shin Ishikane, Fumi Takahashi 産業医科大・医・薬理学 産医大・医・薬理 Systemic sclerosis (SSc) is a connective tissue disorder characterized by skin fibrosis. Currently, there are no topical treatments available for the skin manifestations. We previously reported that celecoxib, a selective inhibitor of COX-2, suppressed cardiac fibrosis. In this study, therefore, we explored the potential of celecoxib as a topical treatment for SSc-related skin fibrosis. We found that celecoxib reduced skin fibrosis and maintained the subcutaneous fat layer in bleomycin-induced scleroderma model mice by topical treatment. To understand the underlying mechanism, we conducted in vitro experiments using 3T3-L1 murine preadipocyte cells. We found that celecoxib inhibited transforming growth factor β (TGF-β)-induced α- smooth muscle actin expression as well as extracellular matrix (ECM) genes, indicating that celecoxib hindered the differentiation of preadipocytes into myofibroblasts. Notably, celecoxib achieved it by downregulating YAP/TAZ signaling pathway, rather than TGF-β/SMAD signaling pathway. The involvement of YAP/TAZ signaling pathway was further confirmed by siRNA-based knockdown of YAP/TAZ. Our findings suggest that topical celecoxib application could be a promising treatment for SSc-related skin fibrosis.