Characterization of SIS3, a novel specific inhibitor of Smad3, and its effect on transforming growth factor-β1-induced extracellular matrix expression

摘要: This is the first report that characterizes specific inhibitor of Smad3 (SIS3) as a potent and selective function. In reporter assay, increased luciferase activity p3TP-lux by overexpression constitutively active form ALK-5 was abrogated treatment with SIS3 in dose-dependent manner. Immunoprecipitation revealed attenuated transforming growth factor (TGF)-beta1-induced phosphorylation interaction Smad4. On other hand, this reagent did not affect Smad2. Thereafter, we evaluated ability suppression TGF-beta1-induced type I procollagen up-regulation human dermal fibroblasts. We found addition effects TGF-beta1 reducing transcriptional activity. also inhibited myofibroblast differentiation fibroblasts TGF-beta1. Moreover, demonstrated completely diminished constitutive well up-regulated collagen expression scleroderma Together, our study suggested useful tool to evaluate TGF-beta-regulated cellular mechanisms via inhibition Smad3.