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.
Antidiuretic action of collecting duct (pro)renin receptor downstream of vasopressin/EP4 receptor. Wang F, Lu X, Peng K, Fang H, Zhou L, Su J, Nau A, Yang K, Ichihara A, Lu A, Zhou SF, Yang T. J Am Soc Nephrol. 2016 Oct;27(10):3022-3034.
Soluble (pro)renin receptor via β-catenin enhances urine concentration capability as a target of liver X receptor. Lu X, Wang F, Xu C, Soodvilai S, Peng K, Su J, Zhao L, Yang KT, Feng Y, Zhou SF, Gustafsson J-A, Yang T. Proc Natl Acad Sci USA. 2016 Mar 29;113(13):E1898-906.
Activation of renal (pro)renin receptor contributes to high fructose-induced salt sensitivity. Xu C, Lu A, Lu X, Zhang L, Fang H, Zhou L, Yang T. Hypertension. 2017 Feb;69(2):339-348.
Prostaglandin E-prostanoid4 receptor mediates angiotensin II-induced (pro)renin receptor expression in the rat renal medulla. Wang F, Lu X, Peng K, Zhou L, Li C, Zhang A, Yang T. Hypertension. 2014 Aug;64(2):369-77.
Site-1 protease-derived soluble (pro)renin receptor targets vasopressin receptor 2 to enhance urine concentrating capability. Wang F, Xu C, Luo R, Peng K, Ramkumar N, Xie S, Lu X, Zhao L, Zuo C-J, Kohan DE, Yang T. JCI Insight. 2019 Apr 4;4(7):e124174.
COX-2-independent activation of penal (pro)renin receptor contributes to DOCA-salt hypertension in rats. Wang F, Sun Y, Luo R, Lu X, Yang B, Yang T. Am J Physiol Renal Physiol. 2020 Oct 1;319(4):F647-F653.
Soluble (pro)renin receptor promotes fibrotic response in renal proximal tubule epithelial cells in vitro via Akt/β-catenin/Snail signaling pathway. Xie S, Su J, Lu A, Lai Y, Mo S, Pu M, Yang T. Am J Physiol Renal Physiol. 2020 Nov 1;319(5):F941-F953.
(Pro)renin receptor decoy peptide PRO20 protects against adriamycin-induced nephropathy by targeting intrarenal renin-angiotensin system. Luo R, Yang K, Wang F, Xu C, Yang T. Am J Physiol Renal Physiol. 2020 Nov 1;319(5):F930-F940.
Soluble (pro)renin receptor regulation of ENaC involved in aldosterone signaling in cultured collecting duct cells. Wang F, Luo R, Peng K, Liu X, Xu C, Lu X, Soodvilai S, Yang T. Am J Physiol Renal Physiol. 2020 Mar 1;318(3):F817-F825.
Site-1 protease-derived soluble (pro)renin receptor contributes to angiotensin II-induced hypertension in mice. Feng Y, Peng K, Luo R, Wang F, Yang T. Hypertension. 2021 Feb;77(2):405-416.
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.
Soluble (pro)renin receptor induces endothelial dysfunction and hypertension in mice with diet-induced obesity via activation of angiotensin II type 1 receptor. Fu Z, Wang F, Liu X, Hu J, Su J, Lu X, Lu A, Cho JM, Symons JD, Zou CJ, Yang T. Clin Sci (Lond). 2021 Mar 26;135(6):793-810.
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.