title: Pigment epithelium-derived factor reduces the PDGF-induced migration and proliferation of human aortic smooth muscle cells through PPARγ activation.
abstract: Our previous study demonstrated that pigment epithelium-derived factor (PEDF) plays an important role in the proliferation and migration of human aortic smooth muscle cells (HASMCs). In the present study, we examined whether PEDF inhibited platelet-derived growth factor (PDGF)-stimulated HASMC migration and proliferation. PEDF dose-dependently reduced PDGF-induced HASMC migration and proliferation in vitro and also arrested cell cycle progression in the G0/G1 phase, and this was associated with decreased expression of cyclin D1, cyclin E, CDK2, CDK4, and p21(Cip1) and increased expression of the cyclin-dependent kinase inhibitor p27(Kip1). The antiproliferative and antimigratory effects of PEDF were partially blocked by the PPARγ antagonist GW9662, but not by the PPARα antagonist MK886. In in vivo studies, the femoral artery of C57BL/6 mice was endothelial-denuded and the mice injected intravenously with PEDF or vehicle. After 2 weeks, both the neointima/media area ratio and cell proliferation (proliferating cell nuclear antigen-positive cells) in the neointima were significantly reduced and again these effects were partially reversed by GW9662 pretreatment. Our data show that PEDF increases PPARγ activation, preventing entry of HASMCs into the cell cycle in vitro and reducing the neointimal area and cell proliferation in the neointima in vivo. Thus, PEDF may represent a safe and effective novel target for the prevention and treatment of vascular proliferative diseases.
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Shu-Huei
authors.initials: SH
authors.lastname: Wang
authors.forename: Chan-Jung
authors.initials: CJ
authors.lastname: Liang
authors.forename: Jiahn-Chun
authors.initials: JC
authors.lastname: Wu
authors.forename: Jiuan-Jiuan
authors.initials: JJ
authors.lastname: Huang
authors.forename: Hsiung-Fei
authors.initials: HF
authors.lastname: Chien
authors.forename: Jaw-Shiun
authors.initials: JS
authors.lastname: Tsai
authors.forename: Yuh-Siu
authors.initials: YS
authors.lastname: Yen
authors.forename: Ying-Chih
authors.initials: YC
authors.lastname: Tseng
authors.forename: June-Horng
authors.initials: JH
authors.lastname: Lue
authors.forename: Yuh-Lien
authors.initials: YL
authors.lastname: Chen
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology; D002453:Cell Cycle / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005136:Eye Proteins / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D058426:Neointima / Q000378:metabolism; D009414:Nerve Growth Factors / Q000494:pharmacology*; D047495:PPAR gamma / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D015843:Serpins / Q000494:pharmacology*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D047495:PPAR gamma; D010982:Platelet-Derived Growth Factor; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor