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 cathB 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 cathB 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 16 h 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 cathB gene expression in renal JG cells are differentially regulated.
Todorov
V
V
Institut für Physiologie I, Universität Regensburg, Deutschland. vladimir.todorov@vkl.uni-regensburg.de
Müller
M
M
Kurtz
A
A
D000804:Angiotensin II / Q000096:biosynthesis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000235:genetics; D002401:Cathepsin B / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D004039:Diet, Sodium-Restricted; D004790:Enzyme Induction; D004792:Enzyme Precursors / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000235:genetics; D007606:Juxtaglomerular Apparatus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000096:biosynthesis* / Q000235:genetics; D012084:Renin-Angiotensin System / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014882:Water-Electrolyte Balance / Q000235:genetics
D000806:Angiotensin-Converting Enzyme Inhibitors; D004792:Enzyme Precursors; D012333:RNA, Messenger; D000804:Angiotensin II; D002401:Cathepsin B; D012083:Renin; D017257:Ramipril; D013755:Tetradecanoylphorbol Acetate