RGD Reference Report - Prorenin and (pro)renin receptor: a review of available data from in vitro studies and experimental models in rodents. - Rat Genome Database

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Prorenin and (pro)renin receptor: a review of available data from in vitro studies and experimental models in rodents.

Authors: Nguyen, G  Danser, AH 
Citation: Nguyen G and Danser AH, Exp Physiol. 2008 May;93(5):557-63. Epub 2008 Mar 30.
RGD ID: 5132617
Pubmed: PMID:18376005   (View Abstract at PubMed)
DOI: DOI:10.1113/expphysiol.2007.040030   (Journal Full-text)

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.

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
renin-angiotensin cascade pathway   TAS 5132617 RGD 
renin-angiotensin cascade pathway   ISOATP6AP2 (Homo sapiens)5132617; 5132617 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Atp6ap2  (ATPase H+ transporting accessory protein 2)

Genes (Mus musculus)
Atp6ap2  (ATPase, H+ transporting, lysosomal accessory protein 2)

Genes (Homo sapiens)
ATP6AP2  (ATPase H+ transporting accessory protein 2)

Additional Information