Pigment epithelium-derived factor reduces the PDGF-induced migration and proliferation of human aortic smooth muscle cells through PPARγ activation

Shu-Huei Wang, Chan-Jung Liang, Jiahn-Chun Wu, Jiuan-Jiuan Huang, Hsiung-Fei Chien, Jaw-Shiun Tsai, Yuh-Siu Yen, Ying-Chih Tseng, June-Horng Lue, Yuh-Lien Chen

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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. © 2011 Elsevier Ltd. All rights reserved.
Original languageEnglish
Pages (from-to)280-289
Number of pages10
JournalInternational Journal of Biochemistry and Cell Biology
Volume44
Issue number2
DOIs
Publication statusPublished - 2012
Externally publishedYes

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Keywords

  • Cell cycle
  • Neointimal hyperplasia
  • PEDF
  • PPARγ
  • Proliferation
  • 2 chloro 5 nitrobenzanilide
  • cyclin D1
  • cyclin dependent kinase 2
  • cyclin dependent kinase 4
  • cyclin dependent kinase inhibitor 1
  • cyclin dependent kinase inhibitor 1B
  • cyclin E
  • cycline
  • peroxisome proliferator activated receptor gamma
  • pigment epithelium derived factor
  • platelet derived growth factor
  • animal experiment
  • animal model
  • animal tissue
  • antiproliferative activity
  • aorta media
  • artery intima proliferation
  • article
  • blood vessel injury
  • cell cycle G0 phase
  • cell cycle progression
  • cell migration
  • cell proliferation
  • concentration response
  • controlled study
  • femoral artery
  • G1 phase cell cycle checkpoint
  • human
  • human cell
  • male
  • mouse
  • neointima
  • nonhuman
  • protein expression
  • smooth muscle fiber
  • Western blotting
  • Animals
  • Aorta
  • Cell Cycle
  • Cell Movement
  • Cell Proliferation
  • Eye Proteins
  • Humans
  • Mice
  • Muscle, Smooth, Vascular
  • Neointima
  • Nerve Growth Factors
  • Platelet-Derived Growth Factor
  • PPAR gamma
  • Serpins
  • Mus

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