Down-regulation of PTEN expression in kidney and its role in development of diabetic nephropathy in rats / 生理学报

ABSTRACT

Transforming growth factor-β1 (TGF-β1)-activated phosphoinositide-3-kinase (PI3K)-protein kinase B (PKB/Akt) pathway is intimately related to the development of diabetic nephropathy (DN), which is negatively regulated by phosphatase and tensin homolog deleted on chromosome ten (PTEN). The present study was to investigate the expression of PTEN in the renal tissue of diabetic mellitus (DM) rats and explore its possible effect on development of DN. Sixteen Sprague-Dawley rats were divided into normal control group (n = 8) and diabetic group (n = 8) at random. Streptozotocin injection was used to establish diabetic model. After 12 weeks, the rats were sacrificed to detect relative biochemical parameters and renal index, and to observe the changes of pathomorphology by HE staining as well. In addition, immunohistochemistry staining and Western blotting were employed to detect the protein expression of PTEN, TGF-β1, PI3Kp110α, Akt1, p-Akt1 (Ser(473)), fibronectin (FN) and Collagen IV, respectively. Furthermore, the expression of PTEN mRNA was also examined by RT-PCR. The results indicated that the levels of blood glucose, serum creatinine and urine protein (24 h) were increased remarkably in the diabetic group (P < 0.05) compared with those in the control group. Compared with those in the control group, the protein expressions of TGF-β1, PI3Kp110α, Akt1 in renal tubular epithelium and the expressions of FN and CollagenIV in renal interstitium were increased in the diabetic group (P < 0.05). The expression of PTEN in the diabetic group was significantly reduced than that in the control group (P < 0.05), and the expression of p-Akt1 (Ser(473)) increased remarkably in the diabetic group which had the similar trend to Akt1 (P < 0.05). PTEN mainly located in renal tubular epithelial cells. The expression of PTEN had negative correlation to that of p-Akt1 (Ser(473)). Compared with that in the control group, the expression of PTEN mRNA was decreased remarkably in the diabetic group (P < 0.05). The data suggest that the down-regulation of PTEN in renal tissue of DM rats may promote the PI3K-PKB/Akt pathway over-activated by TGF-β1, which facilitates the initiation and development of DN.