A KDM6A-KLF10 reinforcing feedback mechanism aggravates diabetic podocyte dysfunction

ABSTRACT: Diabetic nephropathy is the leading cause of end-stage renal disease. Although dysfunction of podocytes, also termed glomerular visceral epithelial cells, is critically associated with diabetic nephropathy, the mechanism underlying podocyte dysfunction still remains obscure. Here, we identify that KDM6A, a histone lysine demethylase, reinforces diabetic podocyte dysfunction by creating a positive feedback loop through up-regulation of its downstream target KLF10. Overexpression of KLF10 in podocytes not only represses multiple podocyte-specific markers including nephrin, but also conversely increases KDM6A expression. We further show that KLF10 inhibits nephrin expression by directly binding to the gene promoter together with the recruitment of methyltransferase Dnmt1. Importantly, inactiv

SUBMITTER: Prof. Chun-Liang Lin 

PROVIDER: S-SCDT-EMM-2018-09828 | biostudies-other |

REPOSITORIES: biostudies-other