Department of Pathophysiology, Faculty of Medicine, Nantong University, Nantong 226001, China.
All-trans retinoic acid inhibits the increases in fibronectin and PAI-1 induced by TGF-β1 and Ang II in rat mesangial cells1
Article first published online: 3 SEP 2008
© 2008 CPS and SIMM
Acta Pharmacologica Sinica
Volume 29, Issue 9, pages 1035–1041, September 2008
How to Cite
LIU, X., LÜ, L., TAO, B.-b. and ZHU, Y.-c. (2008), All-trans retinoic acid inhibits the increases in fibronectin and PAI-1 induced by TGF-β1 and Ang II in rat mesangial cells. Acta Pharmacologica Sinica, 29: 1035–1041. doi: 10.1111/j.1745-7254.2008.00849.x
This work was supported by the National Natural Science Foundation of China (No 30270548) and the Natural Science Foundation of High Education of Jiangsu Province (No 07KJD310171).
- Issue published online: 3 SEP 2008
- Article first published online: 3 SEP 2008
- Received 2008-05-06Accepted 2008-06-17
- plasminogen activator inhibitor 1;
- transforming growth factor beta 1;
- angiotensin II;
- mesangial cells
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 transforming 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 stimulation of TGF-β1 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-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 mesangial cells. The data also suggest that this effect of atRA is associated with a change in PAI-1 levels.