Klotho inhibits PKCα/p66SHC-mediated podocyte injury in diabetic nephropathy

Publication date: Available online 14 June 2019Source: Molecular and Cellular EndocrinologyAuthor(s): Wei Jiang, Tangli Xiao, Wenhao Han, Jiachuan Xiong, Ting He, Yong Liu, Yinghui Huang, Ke Yang, Xianjin Bi, Xinli Xu, Yanlin Yu, Yan Li, Jun Gu, Jingbo Zhang, Yunjian Huang, Bo Zhang, Jinghong ZhaoAbstractDiabetic nephropathy (DN) is a progressive disease, the main pathogeny of which is podocyte injury. As a calcium-dependent serine/threonine protein kinase involved in podocyte injury, protein kinase C isoform α (PKCα) was reported to regulate the phosphorylation of p66SHC. However, the role of PKCα/p66SHC in DN remains unknown. Klotho, an anti-aging protein with critical roles in protecting kidney, is expressed predominantly in the kidney and secreted in the blood. Nonetheless, the mechanism underlying amelioration of podocyte injury by Klotho in DN remains unclear. Our data showed that Klotho was decreased in STZ-treated mice and was further declined in diabetic KL ± mice. As expected, Klotho deficiency aggravated diabetes-induced proteinuria and podocyte injury, accompanied by the activation of PKCα and p66SHC. In contrast, overexpression of Klotho partially ameliorated PKCα/p66SHC-mediated podocyte injury and proteinuria. In addition, in vitro experiments showed that activation of PKCα and subsequently increased intracellular reactive oxygen species (ROS) was involved in podocytic apoptosis induced by high glucose (HG), which coul...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research

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Source: The Tohoku Journal of Experimental Medicine - Category: Research Authors: Tags: Tohoku J Exp Med Source Type: research
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Source: EurekAlert! - Medicine and Health - Category: International Medicine & Public Health Source Type: news
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Source: Clinical Nephrology - Category: Urology & Nephrology Authors: Tags: Clin Nephrol Source Type: research
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