Tissue angiotensin generation depends on the uptake of circulating (kidney-derived) renin and/or its precursor prorenin [together denoted as (pro)renin]. Since tissue renin levels are usually somewhat higher than expected based upon the amount of (renin-containing) blood in tissue, an active uptake mechanism has been proposed. Several candidates have been evaluated in the past three decades, including a renin-binding protein, the mannose 6-phosphate/insulin-like growth factor II receptor and the (pro)renin receptor. Although the latter seemed the most promising, its nanomolar affinity for renin and prorenin is several orders of magnitude above their actual (picomolar) levels in blood, raising doubt on whether (pro)renin–(pro)renin receptor interaction will ever occur in vivo. A wide range of in vitro studies have now demonstrated (pro)renin-receptor-induced effects at nanomolar renin and prorenin concentrations, resulting in a profibrotic phenotype. In addition, beneficial in vivo effects of the putative (pro)renin receptor blocker HRP (handle region peptide) have been observed, particularly in diabetic animal models. Despite these encouraging results, many other studies have reported either no or even contrasting effects of HRP, and (pro)renin-receptor-knockout studies revealed lethal consequences that are (pro)renin-independent, most probably due to the fact that the (pro)renin receptor co-localizes with vacuolar H+-ATPase and possibly determines the stability of this vital enzyme. The present review summarizes all of the recent findings on the (pro)renin receptor and its blockade, and critically compares it with the other candidates that have been proposed to mediate (pro)renin uptake from blood. It ends with the conclusion that the (pro)renin–(pro)renin receptor interaction, if it occurs in vivo, is limited to (pro)renin-synthesizing organs such as the kidney.
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Review Article|
April 05 2012
(Pro)renin and its receptors: pathophysiological implications
Wendy W. Batenburg;
Wendy W. Batenburg
1Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, The Netherlands
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A. H. Jan Danser
1Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Erasmus MC, 3015 GE Rotterdam, The Netherlands
Correspondence: Professor A.H. Jan Danser (email [email protected]).
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Publisher: Portland Press Ltd
Received:
January 24 2012
Revision Received:
February 14 2012
Accepted:
February 17 2012
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2012 Biochemical Society
2012
Clin Sci (Lond) (2012) 123 (3): 121–133.
Article history
Received:
January 24 2012
Revision Received:
February 14 2012
Accepted:
February 17 2012
Citation
Wendy W. Batenburg, A. H. Jan Danser; (Pro)renin and its receptors: pathophysiological implications. Clin Sci (Lond) 1 August 2012; 123 (3): 121–133. doi: https://doi.org/10.1042/CS20120042
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