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- Title
PPARδ inhibits IL-1β-stimulated proliferation and migration of vascular smooth muscle cells via up-regulation of IL-1Ra.
- Authors
Kim, H. J.; Kim, M. Y.; Hwang, J. S.; Lee, J. H.; Chang, K. C.; Han, C. W.; Kim, J.-H.; Seo, H. G.
- Abstract
Activation of peroxisome proliferator-activated receptor (PPAR) δ by GW501516, a specific PPARδ ligand, significantly inhibited interleukin (IL)-1β-induced proliferation and migration of vascular smooth muscle cells (VSMCs). This effect of GW501516 was dependent on transforming growth factor-β, and was mediated through the up-regulation of IL-1 receptor antagonist. The inhibitory effect of GW501516 on VSMC proliferation was associated with cell cycle arrest at the G1 to S phase transition, which was accompanied by the induction of p21 and p53 along with decreased cyclin-dependent kinase 4 expression. Inhibition of cell migration by GW501516 was associated with the down-regulation of matrix metalloproteinase (MMP)-2 and MMP-9 in IL-1β-treated VSMCs. Inhibition of extracellular signal-regulated kinase significantly reduced the GW501516-mediated inhibition of IL-1β-stimulated VSMC proliferation. These results suggest that PPARδ plays an important role in the pathophysiology of diseases associated with the proliferation and migration of VSMCs.
- Subjects
PEROXISOMES; CELL proliferation; TRANSFORMING growth factors; INTERLEUKIN-1; P53 protein
- Publication
Cellular & Molecular Life Sciences, 2010, Vol 67, Issue 12, p2119
- ISSN
1420-682X
- Publication type
Article
- DOI
10.1007/s00018-010-0328-4