Epithelial-to-mesenchymal transdifferentiation of renal tubular epithelial cells mediated by oxidative stress and intervention effect of probucol in diabetic nephropathy rats
10.3760/cma.j.issn.1001-7097.2011.01.006
- VernacularTitle:氧化应激介导糖尿病大鼠肾小管上皮细胞转分化及普罗布考的干预作用
- Author:
Shaobin DUAN
;
Yuhui WANG
;
Fuyou LIU
;
Qiaoyan ZHOU
;
Fang LIU
;
Ying LI
;
Guanghui LING
;
Ying LI
;
Lin SUN
- Publication Type:Journal Article
- Keywords:
Diabetic nephropathy;
Oxidative stress;
Tubular epithelial cell;
Epithelial-to-mesenchymal transdifferentiation;
Probucol
- From:
Chinese Journal of Nephrology
2011;27(1):23-28
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of oxidative stress in the epithelial-tomesenchymal transition (EMT) of tubular epithelial cells and the protective effect of probucol in rat model with diabetic nephropathy (DN). Methods Thirty SD rats were randomly divided into normal control group, DN group, probucol treatment group (supplemented 1% probucol dietary). Twentyfour hours urinary protein excretion (UTP) was measured at the 3rd, the 8th and the 12th week respectively. The biochemical indicators including blood glucose (BG), lipids [triglyceride (TG), total cholesterol (TC)], low-density lipoprotein (LDL), serum creatinine (Scr), creatinine clearance rate (Ccr),kidney tissue malondialdehyde (MDA) level and glutathione peroxidase (GSH-Px) activity were assessed at the end of the 12th week in all groups. The renal pathological changes were evaluated by hematoxylin & eosin (HE) and Masson staining. The protein expression of specificity protein 1 (Sp1), α-smooth muscle actin (α-SMA) and E-cadherin was also detected and analyzed by immunohistochemistry and Western blotting. Results Compared with the normal control group,the BG, TC, LDL, Scr, 24 h UTP and MDA level of renal tissue increased significantly and the Ccr reduced in the rats of DN group (all P＜0.01). The pathological scores and the expression of Sp1 and α-SMA in renal tissue were higher in the DN animals than that in the other animals (all P＜0.01), the expression of E-cadherin downregulated significantly in the DN animals (P＜0.01). The MDA level of renal tissue was positively correlated to the expression of α-SMA and Sp1 protein in DN group (r=0.896, P＜0.01; r=0.862, P＜0.01, respectively), and negatively correlated to the expression of E-cadherin protein (r=-0.673, P＜0.01). In the diabetic animals treated with probucol, the Scr, 24 h UTP, pathological scores, MDA content,expression of Sp1 and α-SMA in renal tissue were lower than those in the diabetic animals (all P＜0.01). The Ccr and the expression of E-cadherin upregulated obviously (all P＜0.01). Conclusion Oxidative stress plays an important role in the EMT process of tubular epithelial cells. Probucol can slow down renal disease progression in DN rats through anti-oxidant, downregulating the expression of Sp1 protein and inhibiting the renal tubular EMT.
