PAN Sunlei1,2, LIN Hui1,2, MENG Liping2, ZHOU Changzuan1,2, JI Zheng2, CHI Jufang2, GUO Hangyuan1,2.
1.The First Clinical Medical College, Wenzhou Medical University, Wenzhou, 325035; 2.Department of Cardiology, Shaoxing People’s Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing, 312000
Abstract：Objective: To explore whether folic acid through the mammalian target of rapamycin (mTOR)/P70S6K signaling pathway to inhibit platelet derived growth factor (PDGF-BB) induced vascular smooth muscle cells (VSMCs) dedifferentiate. Methods: SD rats aortic VSMCs primary cells were cultured and identified, and the 3-7th generations of cells were used for the experiment. The VSMCs were divided into 5 groups: control, PDGF-BB (10 ng/mL), PDGF-BB+1 μmol/L folic acid, PDGF-BB+10 μmol/L folic acid, PDGF-BB+100 μmol/L folic acid. MTT method was used to detection the proliferation of VSMCs in each group. The migratory ability of VSMCs were determined by Wound-Healing assay and Transwell chambers assay. Western blot was used to investigated the expressions of alpha-smooth muscle actin (α-SMA), calponin (Cal), osteopontin (OPN), mTOR, p-mTOR, P70S6K and p-P70S6K in each group. Results: Compared with the control group, the proliferation, migration and the expression of OPN, p-mTOR and p-P70S6K were increased significantly in the VSMCs of PDGF-BB group (<0.05), and the expression of α-SMA and Cal significantly decreased in the VSMCs of PDGF-BB group (P<0.05). Compared with the PDGF-BB group, the proliferation, migration and the expression of OPN, p-mTOR and p-P70S6K were decressed significantly in the VSMCs of each folic acid group (P<0.05), and the expression of α-SMA and Cal significantly increased in the VSMCs of each folic acid group (P<0.05). Folic acid inhibited the PDGF-BB induceing VSMCs dedifferentiation in a dose-dependent manner. Conclusion: Folic acid may inhibit the differentiation of VSMCs induced by PDGF-BB through suppression mTOR/P70S6k signaling pathway.
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