The biology of the (pro)renin receptor.
The (pro)renin receptor (PRR) binds renin and prorenin, its proenzyme inactive form. Receptor-bound prorenin becomes enzymatically active and binding then activates the MAP kinases ERK1/2 and p38 pathways, leading to upregulation of profibrotic and cyclooxygenase-2 genes independent of angiotensin II generation. These characteristics explain the interest in the potential role of PRR in organ damage in diseases associated with activation of the renin-angiotensin system (RAS), in particular hypertension and diabetes. Although identification of PRR has improved our understanding of the physiology of the tissue RAS, its role in pathology is far from clear. Transgenic animals overexpressing PRR ubiquitously or selectively in smooth-muscle cells develop high BP or glomerulosclerosis, and increased expression of PRR is reported in models of hypertension or kidney damage. However, definitive proof is still lacking for a role for PRR in disease, or by showing improvement of disease by tissue-specific ablation of PRR or by administration of a specific PRR antagonist. Furthermore, the early embryonic lethality seen in PRR-null mice suggests PRR has additional essential cellular functions we do not understand.
Nguyen
Genevieve
G
Institut de la Santé et de la Recherche Médicale, Collège de France, Paris, France. genevieve.nguyen@college-de-france.fr
Muller
Dominik N
DN
D000818:Animals; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D012084:Renin-Angiotensin System / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D000093342:Prorenin Receptor
D011956:Receptors, Cell Surface; D048049:Extracellular Signal-Regulated MAP Kinases; D000093342:Prorenin Receptor