All-trans retinoic acid inhibits the increases in fibronectin and PAI-1 induced by TGF-beta1 and Ang II in rat mesangial cells

Acta Pharmacologica Sinica
Xia LiuYi-chun Zhu

Abstract

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. 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. 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. These results indicate that atRA...Continue Reading

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Citations

Sep 18, 2010·The American Journal of Pathology·Jeffrey B HodginVivette D D'Agati
Sep 3, 2013·British Journal of Pharmacology·A C RankinQ Xu
Jul 9, 2010·PPAR Research·Tamás Roszer, Mercedes Ricote
Mar 25, 2011·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Elke RuttenstockPrem Puri
Jan 3, 2019·American Journal of Physiology. Endocrinology and Metabolism·Masanori TamakiToshio Doi

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