%0 Journal Article
%T Pioglitazone Inhibits the Expressions of p22phox and p47phox in Rat Mesangial Cells In Vitro
%A Shan Wang
%A Shan-dong Ye
%A Wen-jia Sun
%A Yuan-yuan Hu
%J ISRN Endocrinology
%D 2014
%R 10.1155/2014/601352
%X Aim. The purpose of this study was to investigate the effects of pioglitazone on oxidative stress and the expressions of p22phox and p47phox, subunits of NADPH oxidase, in mesangial cells (MCs). Method. Rat mesangial cells were cultured and randomly divided into normal glucose (NG) group, high glucose (HG) group, and pioglitazone group. After 48£¿h exposure, the supernatants and cells were collected. The expressions of p22phox and p47phox in MCs were detected by RT-PCR and western blot. The levels of intracellular ROS were determined by flow cytometry. Coloimetry method was used to detect malondialdehyde (MDA) concentrations and superoxide dismutase (SOD) activities. Results. Compared with the NG group, the expression levels of p22phox, p47phox and ROS significantly increased, the activity of SOD decreased in HG group, while the concentration of MDA greatly increased ( ). Pioglitazone significantly suppressed HG-induced p22phox and p47phox expressions and oxidative stress. The protein and gene expressions of p22phox and p47phox were markedly reduced after pioglitazone treatment, so did the ROS generation. The activities of SOD in MCs increased, while the concentrations of MDA in the supernatant decreased greatly by pioglitazone. Conclusions. Pioglitazone can inhibit HG-induced oxidative stress in MCs through suppressing p22phox and p47phox expressions. 1. Introduction Diabetic nephropathy (DN) is the most common cause of end stage renal failure and is a chronic disease characterized by proteinuria, glomerular hypertrophy, decreased glomerular filtration, and renal fibrosis with loss of renal function. Recent studies have shown that oxidative stress promotes the progression of DN [1, 2]. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the predominant enzyme source for ROS generation, which is composed of five subunits comprising a membrane-associated p22phox, a gp91phox subunit and at least four cytosolic subunits: p47phox, p67phox, p40phox, and rac-1/2. Subunits such as p22phox and p47phox were mainly expressed in the kidney. Mesangial cells (MCs), an inherent cell of kidney, play an important role during the development and progression of chronic kidney disease, including DN [3]. Pioglitazone, one of the peroxisome proliferator-activated receptor-¦Ã (PPAR-¦Ã) agonists, is used clinically in the treatment of type 2 diabetes through its insulin-sensitizing effect. Accumulating evidences suggest that pioglitazone may be beneficial for DN independent of its hypoglycemic effects [4¨C6]. The role of pioglitazone in modulating oxidative stress has
%U http://www.hindawi.com/journals/isrn.endocrinology/2014/601352/