scholarly journals Glyceollins inhibit platelet-derived growth factor-mediated human arterial smooth muscle cell proliferation and migration

2011 ◽  
Vol 107 (1) ◽  
pp. 24-35 ◽  
Author(s):  
Hyo Jung Kim ◽  
Byung-Yoon Cha ◽  
Bongkeun Choi ◽  
Ji Sun Lim ◽  
Je-Tae Woo ◽  
...  

Platelet-derived growth factor (PDGF)-BB can induce abnormal proliferation and migration of vascular smooth muscle cells (VSMC) that are involved in the development of CVD. In our preliminary study, phytoalexin glyceollins (glyceollins I, II and III) isolated from soyabean seeds cultured withAspergillus sojaeshowed strong antioxidant and anti-inflammatory activity. Since antioxidants showed beneficial effects on chronic inflammatory diseases, the purpose of the present study was to examine the effects of glyceollins on PDGF-induced proliferation and migration in human aortic smooth muscle cells (HASMC). Incubation of resting HASMC with glyceollins for 24 h significantly diminished PDGF-increased cell number and DNA synthesis in a dose-dependent manner without any cytotoxicity. In addition to blocking of the PDGF-inducible progression through the G0/G1to the S phase of the cell cycle, glyceollins down-regulated the expression of cyclin-dependent kinase (CDK)2 and cyclin D1, and up-regulated the expression of CDK inhibitors such as p27kip1and p53.Glyceollins also effectively inhibited reactive oxygen species generation and phosphorylation of PDGF receptor-β, phospholipase Cγ1, Akt and extracellular signal-regulated kinase 1/2 by PDGF stimulation. Furthermore, glyceollins were found to inhibit PDGF-induced dissociation of actin filaments and cell migration. Thus, the results suggest that glyceollins could become a potent therapeutic agent for regulating VSMC-associated vascular disease such as atherosclerosis and restenosis after angioplasty.

2013 ◽  
Vol 110 (3) ◽  
pp. 391-400 ◽  
Author(s):  
Hyo Jung Kim ◽  
Byung-Yoon Cha ◽  
In Sil Park ◽  
Ji Sun Lim ◽  
Je-Tae Woo ◽  
...  

Liquorice is one of the botanicals used frequently as a traditional medicine in the West and in the East. Platelet-derived growth factor (PDGF)-BB is involved in the development of CVD by inducing abnormal proliferation and migration of vascular smooth muscle cells. In our preliminary study, dehydroglyasperin C (DGC), an active compound of liquorice, showed strong antioxidant activity. Since phytochemicals with antioxidant activities showed beneficial effects on chronic inflammatory diseases, the present study aimed to investigate the effects of DGC on PDGF-induced proliferation and migration of human aortic smooth muscle cells (HASMC). Treatment of HASMC with DGC for 24 h significantly decreased PDGF-induced cell number and DNA synthesis in a dose-dependent manner without any cytotoxicity, as demonstrated by the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide test and thymidine incorporation. Upon cell cycle analysis, DGC blocked the PDGF-induced progression through the G0/G1 to S phase of the cell cycle, and down-regulated the expression of cyclin-dependent kinase (CDK); 2, cyclin E, CDK4 and cyclin D1. Furthermore, DGC significantly attenuated PDGF-stimulated phosphorylation of PDGF receptor-β, phospholipase C-γ1, AKT and extracellular-regulated kinase 1/2, and DGC inhibited cell migration and the dissociation of actin filaments by PDGF. In a rat vascular balloon injury model, DGC suppressed an excessive reduction in luminal diameters and neointimal formation compared with the control group. These results demonstrate the mechanistic basis for the prevention of CVD and the potential therapeutic properties of DGC.


2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Lin Liu ◽  
Xiaowei Xu ◽  
Jiejie Li ◽  
Xia Li ◽  
Wenli Sheng

Phosphodiesterase 4D (PDE4D) is a member of the large superfamily of phosphodiesterases. PDE4D polymorphisms have been found to associate with ischemic stroke. Proliferation and migration of vascular smooth muscle cells (VSMCs) play a critical role in the pathogenesis of atherosclerosis. In this study, infection of VSMCs with lentivrius particles carrying shRNA direct against PDE4D significantly inhibited platelet-derived growth factor-induced VSMC proliferation and migration, and the inhibitory effects were not associated with global intracellular cAMP level. Our results implicate that PDE4D has an important role in VSMC proliferation and migration which may explain its genetic susceptibility to ischemic stroke.


Sign in / Sign up

Export Citation Format

Share Document