Xia Liu1, Lei Lü, Bei-bei Tao, Yi-chun Zhu. 1. Department of Physiology and Pathophysiology, Key Laboratory of Molecular Medicine of the Ministry of Education, Fudan University Shanghai Medical College, Shanghai 200032, China.
Abstract
AIM: 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. METHODS: 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. RESULTS: 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. CONCLUSION: These results indicate that atRA inhibits the increases in fibronectin that are induced by TGF-beta1 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 (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. METHODS: 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. RESULTS: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. CONCLUSION: These results indicate that atRA inhibits the increases in fibronectin that are induced by TGF-beta1 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.
Authors: Jeffrey B Hodgin; Alain C Borczuk; Samih H Nasr; Glen S Markowitz; Viji Nair; Sebastian Martini; Felix Eichinger; Courtenay Vining; Celine C Berthier; Matthias Kretzler; Vivette D D'Agati Journal: Am J Pathol Date: 2010-09-16 Impact factor: 4.307
Authors: Jonathan M Starkey; Yingxin Zhao; Rovshan G Sadygov; Sigmund J Haidacher; Wanda S Lejeune; Nilay Dey; Bruce A Luxon; Maureen A Kane; Joseph L Napoli; Larry Denner; Ronald G Tilton Journal: PLoS One Date: 2010-06-14 Impact factor: 3.240