Aldosterone up-regulates production of plasminogen activator inhibitor-1 by renal mesangial cells.
In vivo studies have demonstrated that aldosterone is an independent contributor to glomerulosclerosis. In the present study, we have investigated whether aldosterone itself mediated glomerulosclerosis, as angiotensin II (Ang II) did, by inducing cultured renal mesangial cells to produce plasminogen activator inhibitor-1 (PAI-1), and whether these effects were mediated by aldosterone-induced increase in transforming growth factor beta(1) (TGF-beta(1)) expression and cellular reactive oxygen species (ROS) activity. Quiescent rat mesangial cells were treated by aldosterone alone or by combination of aldosterone and spironolactone, Ang II, neutralizing antibody to TGF-beta(1) or antioxidant Nacetylcysteme (NAC). This study indicate that aldosterone can increase PAI-1 mRNA and protein expression by cultured mesangial cells alone, which is independent of aldosterone-induced increases in TGF-beta(1) expression and cellular ROS. The effects on PAI-1, TGF-beta(1) and ROS generation were markedly attenuated by spironolactone, a mineralocorticoid receptor antagonist, which demonstrate that mineralocorticoid receptor (MR) may play a role in mediating these effects of aldosterone.
Yuan
Jun
J
Department of nephrology, Renmin Hospital of Wuhan University, Wuhan, China. stfgp@126.com
Jia
Ruhan
R
Bao
Yan
Y
D000111:Acetylcysteine / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009500:Neutralization Tests; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*
D000906:Antibodies; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D053773:Transforming Growth Factor beta1; D000804:Angiotensin II; D013148:Spironolactone; D000450:Aldosterone; D000111:Acetylcysteine