Wilms’ Tumor Protein WT1(‐KTS) inhibits Renin gene transcription

Abstract

The crucial role of renin in the control of various physiological processes, e.g. blood pressure regulation or hematopoiesis, is well known. We report here that the (-KTS) splice form of the Wilms’ tumor protein (WT1) modulates renin expression by transcriptional control. WT1(-KTS) interacts with a regulatory region (hRENc), 12 kb upstream of the renin promoter, and has a suppressing influence on renin gene transcription. The initial bioinformatical predictions were confirmed by reporter gene, and gel shift approaches. Furthermore, we demonstrate that WT1(-KTS) over-expression in stable transfected HEK293 cells, as well as in transiently transfected cells decreased renin mRNA and protein levels. The insertion of a mutation in the WT1(-KTS) protein, which is associated with the formation of Wilms’ tumor, failed to suppress the reporter gene activity and endogenous renin mRNA, consequently leading to accumulation of renin. These findings indicate that renin gene transcription is under control of WT1(-KTS). Furthermore co-expression of WT1 and Renin could be observed in the AS4.1 cell line which is derived from renin producing juxtaglomerular cells. Our data are in line with clinical findings, showing a hyperreninism in patients suffering from mutations in the WT1 gene.