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

作　　者：Xia LIU Lei LV Bei-bei TAO Yi-chun ZHU 

机构地区：[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 [3]Present address Department of Pathophystology, Faculty of Medicine, Nantong University Nantong 226001, China.

出　　处：《Acta Pharmacologica Sinica》2008年第9期1035-1041,共7页中国药理学报（英文版）

基　　金：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）. Xia LIU, Lei LV, and Yi-chun ZHU designed research; Xia LIU and Bei-bei TAO performed Western blotting and RT-PCR, respectively; Xia LIU and Lei LV analyzed data; Xia LIU and Yi-chun ZHU wrote the paper.

摘　　要：Aim： To investigate the effect of all-trans RA （atRA） on the increases in plasminogen activator inhibitor-1 （PAl-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 glomernlar mesangial cells, atRA pretreatment effectively reduced fibronectin expression in glomernlar 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 ofAng 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.Aim： To investigate the effect of all-trans RA （atRA） on the increases in plasminogen activator inhibitor-1 （PAl-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 glomernlar mesangial cells, atRA pretreatment effectively reduced fibronectin expression in glomernlar 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 ofAng 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.

关 键 词：RETINOIDS plasminogen activator inhibitor 1 FIBRONECTINS transforming growth factor betal angiotensin Ⅱ mesangial cells 

分 类 号：R3[医药卫生—基础医学]