Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah, USA.
Curr Opin Nephrol Hypertens. 2022 Jul 1;31(4):351-357. doi: 10.1097/MNH.0000000000000806. Epub 2022 Jun 10.
The (pro)renin receptor (PRR), also termed as ATPase H+ transporting accessory protein 2 (ATP6AP2), was originally cloned as a specific receptor for prorenin and renin [together called (pro)renin]. Given the wide tissue distribution of PRR, PRR was further postulated to act as a regulator of tissue renin. However, assigning a physiological role of PRR within the renin-angiotensin system (RAS) has been challenging largely due to its pleotropic functions in regulation of embryogenesis, autophagy, and H+ transport. The current review will summarize recent advances in understanding the roles of sPPR within the intrarenal RAS as well as those outside this local system.
Site-1 protease (S1P) is a predominant source of sPPR at least in the kidney. So far most of the known physiological functions of PRR including renal handling of electrolytes and fluid and blood pressure are mediated by sPRR. In particular, sPRR serves as a positive regulator of collecting duct renin to activate the intrarenal RAS during water deprivation or angiotensin-II (AngII) infusion. However, PRR/sPRR can act in renin-independent manner under other circumstances.
S1P-derived sPRR has emerged as a key regulator of kidney function and blood pressure and its relationship with the intrarenal RAS depends on the physiological context.
（前）肾素受体（PRR），也称为 ATP 酶 H+转运辅助蛋白 2（ATP6AP2），最初被克隆为（前）肾素和肾素的特异性受体[统称为（前）肾素]。鉴于 PRR 的广泛组织分布，PRR 进一步被假定为组织肾素的调节剂。然而，由于其在胚胎发生、自噬和 H+转运中的多效性功能，PRR 在肾素-血管紧张素系统（RAS）中的生理作用的分配一直具有挑战性。本综述将总结理解肾内 RAS 内 sPPR 以及该局部系统之外的 sPPR 作用的最新进展。
位点 1 蛋白酶（S1P）至少在肾脏中是 sPPR 的主要来源。到目前为止，PRR 的大多数已知生理功能，包括肾脏对电解质和液体以及血压的处理，都是由 sPRR 介导的。特别是，sPRR 作为集合管肾素的正调节剂，在水剥夺或血管紧张素-II（AngII）输注期间激活肾内 RAS。然而，在其他情况下，PRR/sPRR 可以以肾素非依赖性方式发挥作用。
S1P 衍生的 sPRR 已成为肾脏功能和血压的关键调节剂，其与肾内 RAS 的关系取决于生理环境。
