| First Author | Jiang W | Year | 2019 |
| Journal | Mol Cell Endocrinol | Volume | 494 |
| Pages | 110490 | PubMed ID | 31207271 |
| Mgi Jnum | J:279032 | Mgi Id | MGI:6357427 |
| Doi | 10.1016/j.mce.2019.110490 | Citation | Jiang W, et al. (2019) Klotho inhibits PKCalpha/p66SHC-mediated podocyte injury in diabetic nephropathy. Mol Cell Endocrinol 494:110490 |
| abstractText | Diabetic 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 alpha (PKCalpha) was reported to regulate the phosphorylation of p66SHC. However, the role of PKCalpha/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 PKCalpha and p66SHC. In contrast, overexpression of Klotho partially ameliorated PKCalpha/p66SHC-mediated podocyte injury and proteinuria. In addition, in vitro experiments showed that activation of PKCalpha and subsequently increased intracellular reactive oxygen species (ROS) was involved in podocytic apoptosis induced by high glucose (HG), which could be partially reversed by Klotho. Hence, we conclude that Klotho might inhibit PKCalpha/p66SHC-mediated podocyte injury in diabetic nephropathy. |
