Smads are a family of proteins with similar structure that mediates the numerous effects of the transforming growth factor beta (TGF-β) superfamily, which are critically important for tissue regeneration and homeostasis[1]. The specific inhibitor of Smad3 (SIS3) is a synthesized chemical that specifically inhibits Smad3 with IC50 value of 3 μM[2]. A549 cells were treated with 3 μM of SIS3 for 4h prior to 5 ng/mL TGF-β1 exposure for 48 hours. SIS3 markedly decreased the expression of p-Smad3 that was induced by TGF-β1 but did not affect total Smad3 expression as examined by western blotting assay. The results from immunofluorescence assay also indicated that the A549 cells had an obvious nuclear expression of p-Smad3 with a spindle-shaped-like morphology when treated with TGF-β1 only. However, after the pre-treatment with SIS3, the TGF-β1-induced morphological changes were not significant and the fluorescence intensity of p-Smad3 was weakened mainly in the nucleus[3]. In ureteral obstruction (UUO) BALB/c mouse model, 0.2 and 2 mg/kg of SIS3 was intraperitoneally injected to the mice daily for 1 week, and on the 8th post-operation day, the kidney was harvested. The phosphorylation levels of Smad3 were remarkably decreased after treating with SIS3 and the signal ligand TGF-β1 also showed suppression in a dose dependent level measured by western blotting assay[4].
作用机制
SIS3 can specifically inhibits Smad3 phosphorylation and its binding to Smad4 [4] .
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