Roles of ROS and TGF-?1 in aldosterone-induced production of PAI-1
- VernacularTitle:活性氧和转化生长因子?1在醛固酮上调纤溶酶原激活物抑制剂1中的作用
- Author:
Jun YUAN
;
Ru-Han JIA
;
Yan BAO
;
Guo-Hua DING
;
- Publication Type:Journal Article
- Keywords:
Aldosterone;
Plasminogen activator inhibitor 1;
Transforming growth factor beta;
Reactive oxygen species
- From:
Chinese Journal of Nephrology
2005;0(12):-
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the roles of reactive oxygen species(ROS) and TGF-?1 in aldosterone-induced PAI-1 production.Methods Quiescent rat mesangial cells (MCs) were treated by aldosterone.The level of ROS in MCs induced by aldosterone was measured by confecal laser scanning microscopy and the TGF-?1 activity in the supematant of culture was measured by mink lung epithelial cell (Mvllu) proliferation inhibition MTT assay.Then,before the addition of aldosterone,MCs were pretreated with NAC or TGF-?1 neutralizing antibody to decrease cellular ROS or inhibit activity of TGF-?1 induced by aldosterone respectively.PAI-1 mRNA was examined by semi-quantification RT-PCR and PAI-1 protein by Western blotting.Results The intracellular ROS induced by aldosterone increased by 5-fold compared to that of control group,and the activity of TGF-?1 stimulated by aldosterone increased markedly.TGF-?1 neutralizing antibody and NAC effectively decreased aldosterone-induced PAI-1 mRNA expression by 30% and 32%,and PAI-1 protein expression by 21% and 11%,respectively.However,neither TGF-?1 neutralizing antibody nor NAC alone could regulate aldosterone-induced PAI-1 mRNA and protein expression to normal level in 24 hours.Conclusions ROS and TGF-?1 play important roles in up-regulation of aldosterone- induced PAI-1 in MCs.ROS and TGF-?1 are not the exclusive pathway of PAI-1 expression induced by aldosterone in MCs.