| Literature DB >> 30944256 |
Fei Wang1,2, Chuanming Xu1,2, Renfei Luo1,2, Kexin Peng1,2, Nirupama Ramkumar1, Shiying Xie1,2, Xiaohan Lu1,2, Long Zhao1, Chang-Jiang Zuo1, Donald E Kohan1, Tianxin Yang1,2,3.
Abstract
The antidiuretic hormone vasopressin (AVP), acting through its type 2 receptor (V2R) in the collecting duct (CD), critically controls urine concentrating capability. Here, we report that site-1 protease-derived (S1P-derived) soluble (pro)renin receptor (sPRR) participates in regulation of fluid homeostasis via targeting V2R. In cultured inner medullary collecting duct (IMCD) cells, AVP-induced V2R expression was blunted by a PRR antagonist, PRO20; a PRR-neutralizing antibody; or a S1P inhibitor, PF-429242. In parallel, sPRR release was increased by AVP and reduced by PF-429242. Administration of histidine-tagged sPRR, sPRR-His, stimulated V2R expression and also reversed the inhibitory effect of PF-429242 on the expression induced by AVP. PF-429242 treatment in C57/BL6 mice impaired urine concentrating capability, which was rescued by sPRR-His. This observation was recapitulated in mice with renal tubule-specific deletion of S1P. During the pharmacological or genetic manipulation of S1P alone or in combination with sPRR-His, the changes in urine concentration were paralleled with renal expression of V2R and aquaporin-2 (AQP2). Together, these results support that S1P-derived sPRR exerts a key role in determining renal V2R expression and, thus, urine concentrating capability.Entities:
Keywords: Nephrology; Transport
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Year: 2019 PMID： 30944256 PMCID： PMC6483716 DOI： 10.1172/jci.insight.124174
Source DB: PubMed Journal: JCI Insight ISSN： 2379-3708