Open AccessMorin inhibits PDGF-induced proliferation, migration, and invasion of vascular smooth muscle cells via modulating p27KIP1, AKT, and MMP-9 activities
Author(s) -
SeungShick Shin,
Myunggon Ko,
DaeHwa Noh,
Byungil Hwang,
Yujin Park,
Sung Lyea Park,
Wun-Jae Kim,
SungKwon Moon
Publication year - 2018
Publication title -
general physiology and biophysics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.376
H-Index - 39
eISSN - 1338-4325
pISSN - 0231-5882
DOI - 10.4149/gpb_2018028
Subject(s) - morin , platelet derived growth factor receptor , vascular smooth muscle , protein kinase b , cyclin d1 , microbiology and biotechnology , pi3k/akt/mtor pathway , phosphorylation , cyclin d , chemistry , cancer research , biology , signal transduction , cell cycle , biochemistry , growth factor , cell , endocrinology , medicine , receptor , smooth muscle , pathology
Hyper-proliferation and migration of vascular smooth muscle cells (VSMCs) are closely associated with atherosclerosis. Recently, the flavonol morin has been reported to exhibit potent anti-oxidant and anti-inflammatory activities. Therefore, we investigated molecular mechanisms of morin in VSMCs stimulated by PDGF. Morin effectively inhibited PDGF-stimulated proliferation of VSMCs through a G1 cell-cycle arrest, leading to down-regulation of CDK2, CDK4, cyclin D1, and cyclin E proteins. Interestingly, PDGF markedly down-regulated p27KIP1 protein expression; however, morin treatment restored the p27KIP1expression to the basal level. Morin did not affect phosphorylation of MAPKs (ERK, p38, and JNK); however, phosphorylation of AKT was dramatically suppressed by morin in PDGF-stimulated VSMCs. Using the PI3K inhibitor, LY294002, we revealed that AKT is a key regulator in the inhibitory mechanism of morin against PDGF-induced proliferation of VSMCs. Morin disturbed migratory and invasive potential of VSMCs via suppression of matrix metalloproteinase-9 (MMP-9) activity. Using electrophoretic mobility shift assays, we verified that NF-κB, AP-1, and Sp-1 transcription factors are implicated in the mode of action of morin, which suppresses the MMP-9 activity in PDGF-induced VSMCs. Based on the results, we believe that morin may be a potential therapeutic agent for atherosclerosis without negative side effect.