Inhibitory effect of tranilast on the myofibroblast differentiation of rat mesenchymal stem cells induced by transforming growth factor-1 in vitro

摘要

Mesenchymal stem cell (MSC) transplantation is able to attenuate organ fibrosis; however, increasing evidence has indicated that MSCs may be an important cell source of myofibroblasts, which are vital pathogenic cells in fibrotic diseases. The results of the present study revealed that co-culturing with exogenous transforming growth factor (TGF)-1 can induce the transdifferentiation of cultured rat MSCs into myofibroblasts in vitro. Treatment of the MSCs with tranilast [N-(3,4-dimethoxycinnamoyl)-anthranilic acid] attenuated this fibrotic process. Immunocytochemical staining, western blot analysis, reverse transcription-quantitative polymerase chain reaction analysis and cell viability assays were performed in order to evaluate the molecular mechanisms underlying the effects of tranilast on TGF-1-mediated MSC-to-myofibroblast activation. The results demonstrated that TGF-1 upregulated the expression of -smooth muscle actin (-SMA) and collagen type I, and increased the phosphorylation of mothers against decapentaplegic homolog 3 (Smad3) and extracellular signal-regulated kinase 1/2 (ERK1/2) in the rat MSCs; by contrast, tranilast pretreatment downregulated their expression. Furthermore, the proliferation of MSCs induced by TGF-1 was decreased by pretreatment with tranilast. In conclusion, the results of the present study demonstrated that tranilast treatment markedly suppressed the TGF-1-induced differentiation of cultured rat MSCs into myofibroblasts, potentially by inhibiting the Smad3 and ERK1/2 signaling pathways. Therefore, this may be a potential antifibrotic therapeutic strategy, serving as an adjuvant treatment following transplantation of MSCs.