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Deprecated: Implicit conversion from float 267.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Am+J+Transl+Res 2017 ; 9 (3): 1307-16 Nephropedia Template TP
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Folic acid inhibits dedifferentiation of PDGF-BB-induced vascular smooth muscle cells by suppressing mTOR/P70S6K signaling #MMPMID28386356
Pan S; Lin H; Luo H; Gao F; Meng L; Zhou C; Jiang C; Guo Y; Ji Z; Chi J; Guo H
Am J Transl Res 2017[]; 9 (3): 1307-16 PMID28386356show ga
Objective: Folic acid (FA) supplementation reduces the risk of atherosclerosis and stroke. Phenotypic change from differentiated to dedifferentiated vascular smooth muscle cells (VSMCs) plays an important role in atherosclerosis development; however, the exact mechanisms remain unknown. This study aimed to assess whether FA through mammalian target of rapamycin (mTOR)/P70S6K signaling inhibits platelet derived growth factor (PDGF-BB) induced VSMC dedifferentiation. Methods: VSMCs from primary cultures were identified by morphological observation and ?-smooth muscle actin (?-SM-actin, ?-SMA) immunocytochemistry. Then, VSMCs were induced by PDGF-BB and treated with varying FA concentrations. Rapamycin and MHY-1485 were used to inhibit or activate the mTOR/P70S6K pathway, respectively. Next, MTT, Transwell, and wound healing assays were employed to assess proliferation and migration of VSMCs. In addition, Western blotting was used to evaluate protein levels of ?-SMA, calponin, osteopontin, mTOR, p-mTOR, P70S6K and p-P70S6K in VSMCs. Results: VSMCs showed phenotypic alteration from differentiated to dedifferentiated cells in response to PDGF-BB. MTT, Transwell and wound healing assays showed that FA markedly inhibited proliferation and migration in PDGF-BB-induced VSMCs, in a time and concentration-dependent manner. FA treatment increased the expression levels of the contractile phenotype marker proteins ?-SMA and calponin compared with VSMCs stimulated by PDGF-BB alone. Furthermore, FA significantly suppressed mTOR and P70S6K phosphorylation compared with PDGF-BB alone. Similar to FA, downregulation of mTOR signaling by rapamycin inhibited VSMC dedifferentiation. In contrast, upregulation of mTOR signaling by MHY-1485 reversed the FA-induced inhibition of VSMC dedifferentiation. Conclusion: Folic acid inhibits dedifferentiation of PDGF-BB-induced VSMCs by suppressing mTOR/P70S6K signaling.