Interplay between the Notch and PI3K/Akt pathways in high glucose-induced podocyte apoptosis.

Interplay between the Notch and PI3K/Akt pathways in high glucose-induced podocyte apoptosis. Am J Physiol Renal Physiol. 2013 Nov 13; Authors: Wang XM, Yao M, Liu SX, Hao J, Liu QJ, Gao F Abstract Podocyte apoptosis contributes to the pathogenesis of diabetic nephropathy (DN). However, the mechanisms that mediate high glucose (HG)-induced podocyte apoptosis remain poorly understood. Conditionally immortalized mouse podocytes were cultured in HG medium. A chemical inhibitor or a specific short hairpin RNA (shRNA) vector was used to inhibit the activation of the Notch pathway and the PI3K/Akt pathway in HG-treated podocytes. Western blotting and real-time PCR were used to evaluate the levels of Notch, PI3K/Akt and apoptotic pathway signaling. The apoptosis rate of HG-treated podocytes was assessed by TUNEL and Annexin V/PI staining. In HG-treated podocytes, PI3K/Akt pathway activation prevented podocyte apoptosis in the early stage of HG stimulation and Notch pathway-induced podocyte apoptosis in the late stage of HG stimulation. The inhibition of the Notch pathway or the activation of the PI3K/Akt pathway prevented cell apoptosis in HG-treated podocytes. These findings suggest that the Notch and PI3K/Akt pathways may mediate HG-induced podocyte apoptosis. PMID: 24226527 [PubMed - as supplied by publisher]
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research