Differential regulation of cathepsin B and prorenin gene expression in renal juxtaglomerular cells

Cathepsin B (cathB) is a lysosome cysteine proteinase. It has been suggested to process prorenin to renin in the renin producing juxtaglomerular (JG) cells of the afferent arterioles (AA) of the kidney. Whether caths expression is regulated similarly to prorenin production is yet unknown. We have measured prorenin and cathB mRNA levels as well as cathB protein levels in renal AA of Sprague-Dawley rats subjected to low (0.02% w/w) salt diet and ramipril treatment (10 mg/kg/day), or to normal (0.6%) or high (4%) salt diet. Prorenin and cathB expression were also analyzed in the JG cell line As4.1. Prorenin mRNA levels in animals on normal (plus ramipril), low or high salt diet correlated as 1:10:0.5, respectively, while caths mRNA levels correlated as 1:1:0.6, respectively. Treatment of the As4.1 cells with 100 nM phorbol-12-myristate-13-acetate PMA for 16h inhibited prorenin mRNA expression 3-fold relative to the control conditions. CathB mRNA abundance was not different between the PMA treated and the control As4.1 cells. Western analysis of the cathB protein abundance has shown no difference between the rats on normal and low salt diet, and decrease by 50% in the rats on high salt diet. The results of this study suggest that prorenin and caths gene expression in renal JG cells are differentially regulated. Copyright (C) S2001 S, Karger AG, Basel.