Received March 25, 2008
Revised March 27, 2008
Accepted after revision March 28, 2008
PRORENIN AND (PRO)RENIN RECEPTOR: A REVIEW OF AVAILABLE DATA FROM IN VITRO STUDIES AND EXPERIMENTAL MODELS
Genevieve Nguyen 1*
A Jan Danser 2
1 INSERM U833, College de France
2 Erasmus MC
* To whom correspondence should be addressed. E-mail: genevieve.nguyen{at}college-de-france.fr.
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Abstract |
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The discovery of a (pro)renin receptor [(P)RR] and the introduction of renin inhibitors in the clinic has brought renin and prorenin [referred as (pro)renin] back in the spotlight. The (P)RR binds both renin and its inactive precursor prorenin, and such binding triggers intracellular signaling that up-regulates the expression of profibrotic genes, potentially leading to fibrosis, growth and remodeling. 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 faces, an angiotensin-independent face related to (P)RR-induced intracellular signaling and its downstream effects, and an angiotensin-dependent face related to the increased catalytic activity of receptor-bound (pro)renin. A (P)RR blocker has already been described which blocks both faces, thus preventing diabetic nephropathy, cardiac fibrosis and ocular neovascularization. Ongoing experimental studies should now determine which of the two faces plays the most 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.
Key Words:
Hypertension, Kidney, Renin
