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This Article Full Text Full Text (PDF) All Versions of this Article: 93/5/557    most recent expphysiol.2007.040030v1 Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Nguyen, G. Articles by Danser, A. H. J. Search for Related Content PubMed PubMed Citation Articles by Nguyen, G. Articles by Danser, A. H. J. Related Collections Review Articles Renal

¹ Institut de la Santé et de la Recherche Médicale (INSERM) Unit 833 and Collège de France, 11 place Marcelin Berthelot, 75005, Paris, France ² Pharmacology, Vascular and Metabolic Diseases Sector, Department of Internal Medicine, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, The Netherlands

The discovery of a (pro)renin receptor [(P)RR] and the introduction of renin inhibitors in the clinic have brought renin and prorenin back into the spotlight. The (P)RR binds both renin and its inactive precursor prorenin, and such binding triggers intracellular signalling that upregulates the expression of profibrotic genes, potentially leading to cardiac and renal fibrosis, growth and remodelling. Simultaneously, binding of renin to the (P)RR increases its angiotensin I-generating activity, whereas binding of prorenin allows the ‘inactive’ renin precursor to become fully enzymatically active. Therefore, the (pro)renin receptor system could be considered as having two functions, an angiotensin-independent function related to (P)RR-induced intracellular signalling and its downstream effects and an angiotensin-dependent function related to the increased catalytic activity of receptor-bound (pro)renin. A (P)RR blocker has already been described which blocks both functions, thus preventing diabetic nephropathy, cardiac fibrosis and ocular neovascularization. On-going experimental studies should now determine which of the two functions plays the more important role in pathological situations. The results of these studies are extremely important in view of the clinical use of renin inhibitors, since it is well known that their administration results in increased levels of both renin and prorenin. Although this rise can be interpreted as evidence of effective renin–angiotensin system blockade, it could also result in increased (P)RR activation.

(Received 25 March 2008; accepted after revision 28 March 2008; first published online 30 March 2008)
Corresponding author G. Nguyen: Institut de la Santé et de la Recherche Médicale, (INSERM) Unit 833 and Collège de France, Experimental Medecine Unit, 11 place Marcelin Berthelot, 75005, Paris, France. Email: genevieve.nguyen{at}college-de-france.fr