(Pro)Renin Receptor: A Novel Target for Hypertension, Kidney Disease, and Metabolic Syndrome

Recombinant sPRR ameliorates fatty liver as well as other components of metabolic syndrome in mice with diet-induced obesity. Normal diet (lean); diet-induced obesity (DIO); histidine-tagged sPRR (sPRR-His).
Recombinant sPRR ameliorates fatty liver as well as other components of metabolic syndrome in mice with diet-induced obesity. Normal diet (lean); diet-induced obesity (DIO); histidine-tagged sPRR (sPRR-His).

The enzyme renin plays a role in the development of hypertension (high blood pressure), cardiovascular disease, and kidney disease. Studies in mice and rats unexpectedly uncovered other biological activities of the receptor for renin and its precursor, (pro)renin receptor (PRR).  University of Utah Health researcher Tianxin Yang, MD, PhD, and colleagues have made a series of new discoveries about the function of PRR. They demonstrated that PRR activation stimulates sodium and water retention by the kidney, causing hypertension; over-activation of PRR also causes kidney damage. Targeting this pathway with a compound that blocks PRR is highly effective in treating hypertension and chronic kidney disease in rodents. 

Yang and colleagues also showed that a soluble form of PRR found in the body, sPRR, similarly has multiple functions. In addition to regulating kidneys’ handling of sodium and water, administration of sPRR effectively treats multiple components of metabolic syndrome in mice, including obesity, diabetes, and fatty liver. Yang is now actively developing and testing technologies based on these discoveries to treat various human diseases. 

References:

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Elabela antagonizes intrarenal renin-angiotensin system to lower blood pressure and protects against renal injury. Xu C, Wang F, Chen Y, Xie S, Sng D, Reversade B, Yang T. Am J Physiol Renal Physiol. 2020 May 1;318(5):F1122-F1135.

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Mutagenesis of the cleavage site of (pro)renin receptor abrogates angiotensin II-induced hypertension in mice. Wang F, Chen Y,  Zou C, Luo R, Yang T. Hypertension. In press.