Akt2 Is Involved in Loss of Epithelial Cells and Renal Fibrosis following Unilateral Ureteral ObstructionReportar como inadecuado




Akt2 Is Involved in Loss of Epithelial Cells and Renal Fibrosis following Unilateral Ureteral Obstruction - Descarga este documento en PDF. Documentación en PDF para descargar gratis. Disponible también para leer online.

Obstructive nephropathy is an aggressive form of chronic kidney disease CKD, which is characterized by an epithelial-to-mesenchymal transition EMT and interstitial fibrosis. However, the molecular mechanisms of EMT and fibrosis are complex and not fully understood. In this study, we investigated the contribution of Akt2 to experimental renal EMT and fibrosis using the well-established model of unilateral ureteral obstruction UUO. We found that Akt2 and phosphor p-Akt protein levels were increased in the obstructed kidneys. UUO induced activation of transforming growth factor-β1 TGF-β1 signaling. Importantly, knockout of Akt2 suppressed UUO-induced EMT, kidney fibrosis, increased GSK3β activity, and decreased expression of Snail and β-catenin. Inhibition of GSK3β with LiCl the inhibitor of GSK3β increased the expression of Snail and β-catenin in cultured kidney epithelial cells. Our findings suggest that Akt2 partially contributes to interstitial fibrosis following UUO and that inhibition of this signaling pathway may provide a novel approach of prevent progression of renal fibrosis.



Autor: Aiping Lan, Jing Zhang, Zhicheng Xiao, Xiaogang Peng, Yongfen Qi, Jie Du

Fuente: http://plos.srce.hr/



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