Epigallocatechin-3-gallate inhibits the PDGF-induced VEGF expression in human vascular smooth muscle cells via blocking PDGF receptor and Erk-1/2.
Platelet-derived growth factor (PDGF) has been known to induce vascular endothelial growth factor (VEGF) expression in human vascular smooth muscle cells (hVSMCs). We previously reported that Erk-1/2 and AP-1 pathways are crucial in the PDGF-induced VEGF expression in hVSMCs . In this study, we investigated the effect of epigallocatechin-3-gallate (EGCG), the major green tea catechin, on the PDGF-induced VEGF expression in hVSMCs and the underlying mechanisms. EGCG were found to inhibit dose-dependently the VEGF expression and activation of PDGF receptor, Erk-1/2 and AP-1 induced by PDGF. In addition, cell free studies demonstrated that EGCG could directly inhibit the Erk-1/2 activity. Conditioned media from the hVSMCs treated with PDGF could remarkably stimulate the in vitro growth of human umbilical vein endothelial cells (HUVECs) but the media from the EGCG-pretreated hVSMCs lost its stimulatory activity for HUVEC proliferation. These results suggest that EGCG may exert the anti-angiogenic effect by inhibiting the PDGF-induced VEGF expression at multiple signaling levels.
Park
Jung S
JS
Chonnam University Research Institute of Medical Sciences, Chonnam National University Medical School, Kwangju 501-190, Korea.
Kim
Mi H
MH
Chang
Hee J
HJ
Kim
Ki M
KM
Kim
Seok M
SM
Shin
Boo A
BA
Ahn
Bong W
BW
Jung
Young D
YD
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000187:drug effects; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D014470:Umbilical Cord / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000235:genetics
D020533:Angiogenesis Inhibitors; D016588:Anticarcinogenic Agents; D017077:Culture Media, Conditioned; D010982:Platelet-Derived Growth Factor; D042461:Vascular Endothelial Growth Factor A; D002392:Catechin; C045651:epigallocatechin gallate; D017479:Receptors, Platelet-Derived Growth Factor; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3