,All-trans retinoic acid inhibits the increases in fibronectin and PAI-1 in-duced by TGF-β1 and Ang

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Aim:To investigate the effect of all-trans RA (atRA) on the increases in plas-minogen activator inhibitor-1 (PAI-1) and fibronectin that are induced by trans-forming growth factor-β1 (TGF-β1) 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 stimula-tion of TGF-β1 and Ang Ⅱ. Protein expressions of cell-associated fibronectin and PAI-1 in glomerular mesangial cells were evaluated by West blot analy-sis. mRNA expression of RA receptors in glomerular mesangial cells was exam-ined by RT-PCR. Results: Retinoic acid receptor-α, -γ (RAR-α, -γ) and retinoid X receptor-α, -β, γ (RXR-α, -β, -γ) mRNA were expressed in rat glomerular mesangial cells, atRA pretreatment effectively reduced fibronectin expression in glomerular mesangial cells stimulated with TGF-β1 or Ang Ⅱ for 48 h. TGF-β1 stimulated PAI-1 expression reached a maximum at 5 h. atRA didn’t affect the early (5 h) PAI-1 induction by TGF-β1, 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-β1 and Ang Ⅱ in cultured glomerular me-sangial cells. The data also suggest that this effect of atRA is associated with a change in PAI-1 levels.
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