PMID- 28386356
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 9
IP  - 3
DP  - 2017
TI  - Folic acid inhibits dedifferentiation of PDGF-BB-induced vascular smooth muscle 
      cells by suppressing mTOR/P70S6K signaling.
PG  - 1307-1316
AB  - 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 alpha-smooth muscle actin (alpha-SM-actin, alpha-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 alpha-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 alpha-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.
FAU - Pan, Sunlei
AU  - Pan S
AD  - The First Clinical Medical College, Wenzhou Medical University Wenzhou 325000, 
      Zhejiang, China.
FAU - Lin, Hui
AU  - Lin H
AD  - The First Clinical Medical College, Wenzhou Medical University Wenzhou 325000, 
      Zhejiang, China.
FAU - Luo, Hangqi
AU  - Luo H
AD  - Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of 
      Zhejiang University Shaoxing 312000, Zhejiang, China.
FAU - Gao, Feidan
AU  - Gao F
AD  - Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of 
      Zhejiang University Shaoxing 312000, Zhejiang, China.
FAU - Meng, Liping
AU  - Meng L
AD  - Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of 
      Zhejiang University Shaoxing 312000, Zhejiang, China.
FAU - Zhou, Changzuan
AU  - Zhou C
AD  - Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of 
      Zhejiang University Shaoxing 312000, Zhejiang, China.
FAU - Jiang, Chengjian
AU  - Jiang C
AD  - Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of 
      Zhejiang University Shaoxing 312000, Zhejiang, China.
FAU - Guo, Yan
AU  - Guo Y
AD  - Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of 
      Zhejiang University Shaoxing 312000, Zhejiang, China.
FAU - Ji, Zheng
AU  - Ji Z
AD  - Department of Cardiology, Shaoxing People's Hospital, Shaoxing Hospital of 
      Zhejiang University Shaoxing 312000, Zhejiang, China.
FAU - Chi, Jufang
AU  - Chi J
AD  - The First Clinical Medical College, Wenzhou Medical UniversityWenzhou 325000, 
      Zhejiang, China; Department of Cardiology, Shaoxing People's Hospital, Shaoxing 
      Hospital of Zhejiang UniversityShaoxing 312000, Zhejiang, China.
FAU - Guo, Hangyuan
AU  - Guo H
AD  - The First Clinical Medical College, Wenzhou Medical UniversityWenzhou 325000, 
      Zhejiang, China; Department of Cardiology, Shaoxing People's Hospital, Shaoxing 
      Hospital of Zhejiang UniversityShaoxing 312000, Zhejiang, China.
LA  - eng
PT  - Journal Article
DEP - 20170315
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC5376021
OTO - NOTNLM
OT  - Vascular smooth muscle cells
OT  - dedifferentiation
OT  - folic acid
OT  - mTOR/P70S6K signaling pathway
EDAT- 2017/04/08 06:00
MHDA- 2017/04/08 06:01
PMCR- 2017/03/15
CRDT- 2017/04/08 06:00
PHST- 2016/12/22 00:00 [received]
PHST- 2017/03/07 00:00 [accepted]
PHST- 2017/04/08 06:00 [entrez]
PHST- 2017/04/08 06:00 [pubmed]
PHST- 2017/04/08 06:01 [medline]
PHST- 2017/03/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2017 Mar 15;9(3):1307-1316. eCollection 2017.