title: The interaction between prorenin, renin and the (pro)renin receptor:  time to rethink the role in hypertension.
abstract: OBJECTIVE
  Elevated prorenin levels are seen in diabetics with microvascular disease. The discovery of a receptor capable of binding renin and prorenin [(P)RR] and triggering an intracellular signal in the laboratory setting raised the expectation that prorenin might be directly responsible for these vascular disorders. However, there has been substantial disagreement concerning the signaling properties of renin and prorenin and it has been impossible to inactivate the (P)RR gene in mouse to define its function.
  
  
  RESULTS
  Mouse and rat models in which prorenin is highly overexpressed do not demonstrate the glomerulosclerosis typically seen in severe diabetic nephropathy, but do exhibit an increase in blood pressure that is angiotensin II-dependent. (P)RR has been shown to colocalize with other subunits of the vacuolar ATPase in the kidney and heart and to be necessary for Wnt signaling in a renin-independent manner. Although whole-body inactivation of the (P)RR gene is lethal, tissue-specific inactivation results in severe disorders associated with massive cell death.
  
  
  CONCLUSIONS
  These results do not support a role of direct prorenin or renin signaling through (P)RR in vascular disorders. Rather, they suggest that the main role of (P)RR is as a subunit of the vacuolarATPase complex. Whether or not (P)RR is responsible for the ability of prorenin to generate angiotensin II in tissues has not been resolved.
authors.affiliation: Laboratory of Molecular Biochemistry of Hypertension, Institut de Recherches Cliniques de Montreal and Department of Medicine, Université de Montréal, Montreal, Quebec, Canada. reudelt@ircm.qc.ca
authors.forename: Timothy L
authors.initials: TL
authors.lastname: Reudelhuber
mesh_terms: D000818:Animals; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000209:etiology*; D011956:Receptors, Cell Surface / Q000097:blood*; D012083:Renin / Q000097:blood*; D060449:Wnt Signaling Pathway; D000093342:Prorenin Receptor
chemical_list: D011956:Receptors, Cell Surface; D012083:Renin; D000093342:Prorenin Receptor