Chinese rice wine polyphenol compounds inhibit vascular smooth muscle cell dedifferentiation and its mechanism

Objective: To verify whether Chinese rice wine polyphenol compounds (RWPC) could inhibit rat aortic vascular smooth muscle cells (VSMCs) dedifferentiation through mammalian target of rapamycin (mTOR)/P70S6K pathway. Methods: The primary culture and identification of rat VSMCs was conducted and VSMCs in passages 3-5 were used for the following experiments. Platelet derived growth factor-BB (PDGF-BB) was used to induce VSMCs dedifferentiation. Rapamycin and MHY-1485 were used to inhibit or activate mTOR/P70S6K pathway respectively. After incubation in different concentrations of RWPC, the proliferation and migration ability of the VSMCs were tested by MTT assay, Transwell chambers, and wound healing assay. Western blotting was employed to investigate the expressions of SM-actin, calponin, SM-MHC, OPN, mTOR, p-mTOR, P70S6K and p-P70S6K in VSMCs. Results: PDGF-BB improved the proliferation and migration ability of VSMCs and increased the expression of calponin, SMMHC, p-mTOR, p-P70S6K. RWPC significantly inhibited the induction of these phenotypic changes induced by PDGFBB, Meanwhile RWPC suppressed mTOR signaling in the VSMCs. Identical to RWPC, inhibiting the activity of mTOR signaling by rapamycin could also inhibit VSMC dedifferentiation. In contrast, up-regulation of mTOR signaling by MHY-1485 could reverse the RWPC-induced inhibition of VSMC dedifferentiation. Conclusion: RWPC inhibits VSMCs dedifferentiation by suppressing mTOR/P70S6K signaling pathway.