All-trans retinoic acid inhibits the increases in fibronectin and PAI-1 induced by TGF-beta1 and Ang II in rat mesangial cells.
Acta Pharmacol Sin
; 29(9): 1035-41, 2008 Sep.
Article
en En
| MEDLINE
| ID: mdl-18718172
ABSTRACT
AIM:
To investigate the effect of all-trans RA (atRA) on the increases in plasminogen activator inhibitor-1 (PAI-1) and fibronectin that are induced by transforming growth factor-beta1 (TGF-beta1) and angiotensin II (Ang II) in cultured rat glomerular mesangial cells.METHODS:
Subconfluent glomerular mesangial cells were serum-starved for 48 h and pretreated with atRA with subsequent stimulation of TGF-beta1 and Ang II. Protein expressions of cell-associated fibronectin and PAI-1 in glomerular mesangial cells were evaluated by Western blot analysis. mRNA expression of RA receptors in glomerular mesangial cells was examined by RT-PCR.RESULTS:
Retinoic acid receptor-alpha, -gamma (RAR-alpha, -gamma) and retinoid X receptor-alpha, -beta, -gamma (RXR-alpha, -beta, -gamma) mRNA were expressed in rat glomerular mesangial cells. atRA pretreatment effectively reduced fibronectin expression in glomerular mesangial cells stimulated with TGF-beta 1 or Ang II for 48 h. TGF-beta 1 stimulated PAI-1 expression reached a maximum at 5 h. atRA didn't affect the early (5 h) PAI-1 induction by TGF-beta 1, but markedly attenuated the sustained (48 h) PAI-1 induction. atRA also decreased the prolonged effect of Ang II on PAI-1 expression.CONCLUSION:
These results indicate that atRA inhibits the increases in fibronectin that are induced by TGF-beta1 and Ang II in cultured glomerular mesangial cells. The data also suggest that this effect of atRA is associated with a change in PAI-1 levels.
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MEDLINE
Asunto principal:
Tretinoina
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Angiotensina II
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Fibronectinas
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Inhibidor 1 de Activador Plasminogénico
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Factor de Crecimiento Transformador beta1
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Mesangio Glomerular
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Animals
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Año:
2008
Tipo del documento:
Article