All-trans retinoic acid inhibits the increases in fibronectin and PAI-1 induced by TGF-β1 and Ang II in rat mesangial cells1

Authors

  • Xia LIU,

    1. Department of Physiology and Pathophysiology, Key Laboratory of Molecular Medicine of the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, China
    2. Department of Pathophysiology, Faculty of Medicine, Nantong University, Nantong 226001, China
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    • 4

      Department of Pathophysiology, Faculty of Medicine, Nantong University, Nantong 226001, China.

  • Lei LÜ,

    1. Department of Physiology and Pathophysiology, Key Laboratory of Molecular Medicine of the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, China
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  • Bei-bei TAO,

    1. Department of Physiology and Pathophysiology, Key Laboratory of Molecular Medicine of the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, China
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  • Yi-chun ZHU

    Corresponding author
    1. Department of Physiology and Pathophysiology, Key Laboratory of Molecular Medicine of the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, China
      Correspondence to Prof Yi-chun ZHU. Phn/Fax 86-21-5423-7098. E-mail yczhu@shmu.edu.cn.
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  • 1

    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).

Correspondence to Prof Yi-chun ZHU. Phn/Fax 86-21-5423-7098. E-mail yczhu@shmu.edu.cn.

Abstract

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.

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