IMR Press / FBS / Volume 3 / Issue 4 / DOI: 10.2741/221

Frontiers in Bioscience-Scholar (FBS) is published by IMR Press from Volume 13 Issue 1 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.


HRP and prorenin: focus on the (pro)renin receptor and vacuolar H+-ATPase

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1 Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

*Author to whom correspondence should be addressed.

Academic Editor: Fumiaki Suzuki

Front. Biosci. (Schol Ed) 2011, 3(4), 1205–1215;
Published: 1 June 2011
(This article belongs to the Special Issue Handle region peptide and prorenin receptor)

The function of prorenin, the precursor of renin, remained unknown until the discovery of the (pro)renin receptor ((P)RR). (Pro)renin binding to this receptor allows angiotensin generation and induces signaling. Thus, (P)RR blockade will exert effects beyond angiotensin suppression. Recently, the (P)RR has been identified as an accessory protein of the vacuolar-type H+-ATPase, with important roles in Wnt signaling. In addition, transgenic animals overexpressing prorenin display the consequences of angiotensin generation, whereas transgenic animals overexpressing the (P)RR display an angiotensin-independent phenotype. Finally, both beneficial and deleterious effects have been described following treatment with the (P)RR antagonist 'handle region peptide' (HRP), while a (P)RR knockout in cardiomyocytes is lethal. This review highlights the latest findings in the (P)RR area, focusing on cardiovascular and renal pathology. It critically addresses the possibility that (pro)renin acts as an agonist of this receptor in vivo, and discusses the efficacy of HRP. Conclusions are that convincing evidence for (pro)renin-(P)RR interaction in vivo is currently lacking and, thus, that the concept of HRP exerting beneficial effects by blocking such interaction remains to be proven.

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