P2007 Sulforaphane enhances proliferation of porcine satellite cells through suppression of TGF-β signaling pathway

Abstract

Satellite cells, the muscle stem cells, play a critical role in muscle growth, maintenance, and regeneration. A lot of muscle diseases result from defective function of satellite cells. Porcine satellite cells are a good model for studying the role of satellite cells in muscle development. Sulforaphane (SFN), a natural molecule rich in cruciferous vegetables, is a potent inducer for the NF-E2-related factor 2 (Nrf2) signaling and also inhibits the activity of histone deacetylases (HDAC). Our previous study found that SFN epigenetically suppressed the transcription of myostatin in porcine satellite cells. However, the effects of SFN on the proliferation of porcine satellite cells and the related mechanisms are far from understood. In the present study, we report that SFN enhanced the proliferation of the porcine satellite cells and modified the expression myogenic regulatory factors. SFN altered the expression of HDACs and inhibited the activity of HDACs. The activity of TGF-β signaling was suppressed by SFN treatment, which was accompanied with up-regulated Smad7, an endogenous suppressor of TGF-β signaling. Furthermore, we found that SFN increased the mRNA expression of Smad7’s transcription factors and decreased the expression of miRNAs targeting Smad7. The DNA methylation of a studied fragment in Smad7 promoter was not influenced by SFN treatment. SFN has received substantial attention because of its potential application in cancer therapy. The present study, for the first time, investigated the effects of SFN on the proliferation of porcine satellite cells and the underlying mechanism. We found that both mRNA and protein level of Smad7 were greatly increased by SFN. Thus, besides reducing TGF-β1 protein abundance, SFN also inhibits the activity of TGF-β signaling by increasing expression of Smad7. It has been shown that overexpression of Smad7 led to enhanced skeletal muscle differentiation and cellular hypertrophy. In summary, our studies state that SFN enhances the proliferation of porcine satellite cells by suppressing TGF-β signaling through activation of Smad7.