| Content Provider |
World Health Organization (WHO)-Global Index Medicus |
| Author |
Peng, Kexin Soodvilai, Sunny Lu, Xiaohan Wang, Fei Yang, Kevin T. Feng, Yumei Xu, Chuanming Zhou, Shu-feng Gustafsson, Jan-åke Zhao, Long Su, Jiahui Yang, Tianxin |
| Description |
Author Affiliation: Lu X ( Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112); Wang F ( Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China); Xu C ( Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China); Soodvilai S ( Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112); Peng K ( Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112); Su J ( Institute of Hypertension, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, People's Republic of China); Zhao L ( Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112); Yang KT ( Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112); Feng Y ( Department of Pharmacology, University of Nevada School of Medicine, Reno, NV 89557); Zhou SF ( Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL 33620); Gustafsson JÅ ( Department of Biology and Biochemistry, University of Houston, Houston, TX 77004 jgustafsson@uh.edu Tianxin.Yang@hsc.utah.edu.); Yang T ( Department of Internal Medicine, University of Utah, Salt Lake City, UT 84112); |
| Abstract |
The extracellular domain of the (pro)renin receptor (PRR) is cleaved to produce a soluble (pro)renin receptor (sPRR) that is detected in biological fluid and elevated under certain pathological conditions. The present study was performed to define the antidiuretic action of sPRR and its potential interaction with liver X receptors (LXRs), which are known regulators of urine-concentrating capability. Water deprivation consistently elevated urinary sPRR excretion in mice and humans. A template-based algorithm for protein-protein interaction predicted the interaction between sPRR and frizzled-8 (FZD8), which subsequently was confirmed by coimmunoprecipitation. A recombinant histidine-tagged sPRR (sPRR-His) in the nanomolar range induced a remarkable increase in the abundance of renal aquaporin 2 (AQP2) protein in primary rat inner medullary collecting duct cells. The AQP2 up-regulation relied on sequential activation of FZD8-dependent ß-catenin signaling and cAMP-PKA pathways. Inhibition of FZD8 or tankyrase in rats induced polyuria, polydipsia, and hyperosmotic urine. Administration of sPRR-His alleviated the symptoms of diabetes insipidus induced in mice by vasopressin 2 receptor antagonism. Administration of the LXR agonist TO901317 to C57/BL6 mice induced polyuria and suppressed renal AQP2 expression associated with reduced renal PRR expression and urinary sPRR excretion. Administration of sPRR-His reversed most of the effects of TO901317. In cultured collecting duct cells, TO901317 suppressed PRR protein expression, sPRR release, and PRR transcriptional activity. Overall we demonstrate, for the first time to our knowledge, that sPRR exerts antidiuretic action via FZD8-dependent stimulation of AQP2 expression and that inhibition of this pathway contributes to the pathogenesis of diabetes insipidus induced by LXR agonism. |
| ISSN |
00278424 |
| e-ISSN |
10916490 |
| Journal |
Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number |
13 |
| Volume Number |
113 |
| Language |
English |
| Publisher |
National Academy of Sciences |
| Publisher Date |
2016-04-01 |
| Publisher Place |
United States |
| Access Restriction |
Open |
| Subject Keyword |
Diabetes Insipidus Drug Therapy Orphan Nuclear Receptors Metabolism Receptors, Cell Surface Urine Chemistry Beta Catenin Animals Aquaporin 2 Hydrocarbons, Fluorinated Pharmacology Mice, Inbred C57BL Agonists Osmosis Rats, Sprague-Dawley Genetics Recombinant Proteins Solubility Sulfonamides Physiology Wnt Signaling Pathway Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type |
Text |
| Resource Type |
Article |
| Subject |
Multidisciplinary |
