Renin and prorenin receptor in hypertension: what's new?
The (pro)renin receptor, PRR, was initially characterized as a component of the renin-angiotensin system (RAS). PRR-bound renin and prorenin display increased enzymatic activity, and binding activates intracellular signaling, upregulating the expression of profibrotic proteins. As a consequence, most studies set out to demonstrate a role of PRR in hypertension, cardiovascular and renal diseases, and organ damage, and to identify PRR as a therapeutic target to optimize RAS blockade. The results of animal studies were disappointing and did not convincingly establish PRR as major player in hypertension or in organ damage, although human studies suggested a link between a polymorphism in the PRR gene and blood pressure. New data now suggest that PRR is functionally linked to the vacuolar proton-ATPase and, quite unexpectedly, that PRR is necessary to Wnt signaling pathways that are essential (independently of renin) for adult and embryonic stem cell biology, embryonic development, and diseases including cancer, thereby opening new perspectives on the pathophysiological roles of PRR.
Center for Interdisciplinary Research in Biology and Experimental Medicine Unit Collège de France, Institut National de la Santé et de la Recherche Médicale (INSERM), 11 place Marcelin Berthelot, Paris, France. genevieve.nguyen@college-de-france.fr
Genevieve
G
Nguyen
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors*; D012083:Renin / Q000187:drug effects*; D012084:Renin-Angiotensin System / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D025262:Vacuolar Proton-Translocating ATPases / Q000187:drug effects / Q000378:metabolism; D051153:Wnt Proteins / Q000187:drug effects / Q000378:metabolism; D000093342:Prorenin Receptor
D011956:Receptors, Cell Surface; D051153:Wnt Proteins; D012083:Renin; D025262:Vacuolar Proton-Translocating ATPases; D000093342:Prorenin Receptor