PPARdelta inhibits IL-1beta-stimulated proliferation and migration of vascular smooth muscle cells via up-regulation of IL-1Ra.
Cell Mol Life Sci
; 67(12): 2119-30, 2010 Jun.
Article
en En
| MEDLINE
| ID: mdl-20221783
Activation of peroxisome proliferator-activated receptor (PPAR) delta by GW501516, a specific PPARdelta ligand, significantly inhibited interleukin (IL)-1beta-induced proliferation and migration of vascular smooth muscle cells (VSMCs). This effect of GW501516 was dependent on transforming growth factor-beta, 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-1beta-treated VSMCs. Inhibition of extracellular signal-regulated kinase significantly reduced the GW501516-mediated inhibition of IL-1beta-stimulated VSMC proliferation. These results suggest that PPARdelta plays an important role in the pathophysiology of diseases associated with the proliferation and migration of VSMCs.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ciclo Celular
/
Regulación hacia Arriba
/
Miocitos del Músculo Liso
/
PPAR delta
/
Músculo Liso Vascular
Límite:
Animals
Idioma:
En
Revista:
Cell Mol Life Sci
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2010
Tipo del documento:
Article
Pais de publicación:
Suiza