Professor of Nephrology & Hypertension and Adjunct Professor of Nutrition and Integrative Physiology
(Pro)renin receptor, The Distal Nephron, Hypertension, Kidney Disease, Diabetes
Molecular Biology Program
We are broadly interested in basic and translational research on hypertension and kidney disease as well as metabolic disease. In particular, we focus on defining novel factors such as prostaglandins, nuclear receptors, and (pro)renin receptor in the distal nephron, a unique nephron site critically important for hormonal control of plasma volume and blood pressure. Specifically, we have been studying prostaglandins and other lipid-derived mediators that regulate renal function and blood pressure for a long time. Over the years, we have defined the role of COX-2/mPGES-1/PGE2 pathway, the nuclear receptor PPAR gamma in renal health and disease. Our recent work has demonstrated an important interplay between the lipid mediators and (pro)renin receptor in the distal nephron. Our results suggest that (pro)renin receptor serves as a common downstream pathway leading to fine-tuning urinary Na+ and water excretion and long-term control of blood pressure. Overactivation of renal PRR results in enhancement of intrarenal renin-angiotensin system and renal medullary α-ENaC expression which underlie pathogenesis of hypertension as well as chronic kidney disease. In particular, we for the first time discovered a novel role of soluble (pro)renin receptor (sPRR) in regulation of aquaporin-2 expression and urine concentrating capability (Lu et al. PNAS 2016). We have recently identified site-1 protease as a predominant PRR cleavage protease. The current research focuses on the signaling and function of sPRR under various physio-pathological conditions. We employ integrative experimental approaches involving conditional gene targeting, radiotelemetry measurement of blood pressure, cell culture, molecular biology, mouse renal physiology, as well as drug library screening. Our goal is to translate basic discovery to novel medicines for patients with kidney disease, hypertension, and metabolic disease.
Selected Publications Original studies (selected from a total of 163):
- Xu C, Yang G, Fu Z, Chen Y, Xie S Wang F, and Yang T. Na+-Retaining Action of COX-2/EP1 Pathway in the Collecting Duct via Activation of Intrarenal RAAS and ENaC. In press 2022
- Hu J, Tan Y, Chen Y, Mo S, Hekking B, Su J, Pu M, Lu A, Symons JD, and Yang T. Role of (Pro)Renin Receptor in Cyclosporin A-Induced Nephropathy. Am J Physiol-Renal Physiology In press
- Lu A, Pu M, Mo S, Su J, Hu J, Li C, Wang W, Yang T. (Pro)Renin Receptor Regulates Phosphate Homeostasis in Rats via Releasing Fibroblast Growth Factor-23. Front Physiol. In press 2022
- Xu C, Chen Y, Wang F, Xie S, Yang T. Soluble (Pro)Renin Receptor as a Negative Regulator of NCC Activity. Hypertension (with editorial commentary). 78(4):1027-1038, 2021 doi: 10.1161/HYPERTENSIONAHA.121.16981. PMID: 34495675
- Wang Y, Wang Y, Xue K, Wang H, Zhou J, Gao F, Li C, Yang T, Fang H. (Pro)Renin Receptor Antagonist PRO20 Attenuates Nephrectomy-Induced Nephropathy in Rats via Inhibition of Intrarenal RAS and Wnt/β-Catenin Signaling. Physiological Reports. In press 2021
- Wang F, Chen Y, Zou C, Luo R, and Yang T. Mutagenesis of the Cleavage Site of (Pro)Renin Receptor Abrogates Angiotensin II-Induced Hypertension in Mice. 78:115-127, 2021
- Fu Z, Wang F, Liu X, Hu J, Su J, Lu X, Lu A, Cho JM, Symons JD, Zou CJ, Yang T. Soluble (Pro)Renin Receptor Induces Endothelial Dysfunction and Hypertension in Mice with Diet-Induced Obesity via Activation of Angiotensin II Type 1 Receptor. Clinical Science (Lond). 135:793-810, 2021
- Chen Y, Xu C, Hu JJ, Deng M, Qiu Q, Mo S, Du Y, and Yang T. Diuretic Action of Apelin-13 Mediated by Inhibiting cAMP/PKA/sPRR Pathway. Front Physiol. 12:642274. 2021 doi: 10.3389/fphys.2021.642274.
- Al-Rabadi LF, Caza T, Trivin-Avillach C, Rodan AR, Andeen N, Hayashi N,Williams B, Revelo MP, Clayton F, Abraham J, Lin E, Liou W, Zou CJ, Ramkumar N, Cummins T, Wilkey DW, Kawalit I, Herzog C, Storey A,Edmondson R,Sjoberg R, Yang T, Chien J, Merchant M, Arthur J,Klein J, Larsen C, and Beck, LH Jr. Serine protease HTRA1 as a novel target antigen in primary membranous nephropathy. JASN In press 2021
- Feng Y, Peng K, Luo R, Wang F, and Yang T. Site-1 Protease-Derived Soluble (Pro)Renin Receptor Contributes to Angiotensin II-Induced Hypertension in Mice. Hypertension (with editorial commentary). 77(2):405-416 2021
- Luo R, Yang K, Wang F, Xu C, and Yang T. A (pro)renin receptor decoy peptide PRO20 protects against adriamycin-induced nephropathy by targeting intrarenal renin-angiotensin system. Am J Physiol-Renal Physiology, 319(5):F930-F940. 2020
- Xie S, Su J, Lu A, Lai Y, MoS, PuM, and Yang T. Soluble (pro)renin receptor promotes fibrotic response in renal proximal tubule epithelial cells in vitro via Akt/β-catenin/Snail signaling pathway. Am J Physiol-Renal Physiology. 319(5):F941-F953. 2020 doi: 10.1152/ajprenal.00197.2020.
- Wang F, Sun Y, Luo R, Lu X, Yang B and Yang T. COX-2-independent activation of penal (pro)renin receptor contributes to DOCA-salt hypertension in rats. Am J Physiol-Renal Physiology. 319(4):F647-F653. 2020
- Wang F, Luo R, Peng K, Liu X, Xu C, Lu X, Soodvilai S, and Yang T. Soluble (pro)renin receptor regulation of ENaC involved in aldosterone signaling in cultured collecting duct cells. Am J Physiol-Renal Physiology In press 2020.
- Xu C, Wang F, Chen Y, Xie S, Sng D, Reversade B, and Yang T. Elabela antagonizes intrarenal renin-angiotensin system to lower blood pressure and protects against renal injury. Am J Physiol-Renal Physiology In press 2020.
- Wang F, Luo R, Zou C, Xie S, Peng K, Zhao L, Yang KT, Xu C, and Yang T. Soluble (pro)renin receptor treats metabolic syndrome in mice with diet-induced obesity via interaction with PPARγ. JCI Inishgt. 5(7):e128061 2020. doi: 10.1172/jci.insight.128061.
- Zhang L, Deng M, Lu A, Chen Y, Chen Y, Wu C, Tan Z, Boini KM, Yang T, Zhu Q, Wang L. Sodium butyrate attenuates angiotensin II-induced cardiac hypertrophy by inhibiting COX2/PGE2 pathway via a HDAC5/HDAC6-dependent mechanism. J Cell Mol Med. 23:8139-8150, 2019
- Jian YP, Yuan HX, Hu KH, Chen C, Li YQ, Li Y, Yang T, Ou ZJ, Ou JS. Protein compositions changes of circulating microparticles in patients with valvular heart disease subjected to cardiac surgery contribute to systemic inflammatory response and disorder of Shock. 52:487-496, 2019.
- Zhang L, Deng M, Lu A, Chen Y, Chen Y, Wu C, Tan Z, Boini KM, Yang T, Zhu Q, Wang L.J Cell Mol Med. In press 2019
- Wang F, Xu C, Luo R,Peng K, Ramkumar N, Xie S, Lu X, Zhao L, Zuo C-J, Kohan DE, and Yang T. ,Site-1 protease-derived soluble (pro)renin receptor targets vasopressin receptor 2 to enhance urine concentrating capability. JCI Insight 4;4(7):e124174, 2019
- Fu Z, Hu J, Zhou L, Chen Y, Deng M, Liu X, Su J, Lu A, and Yang T. (Pro)renin receptor contributes to pregnancy-induced sodium-water retention in rats via activation of intrarenal RAAS and α-ENaC. AJP-Renal Physiology In press 2019
- Luo R, Hu S, Liu Q, Han M, Wang F, Qiu M, Li S, Li X, Yang T, Fu X, Wang W, and Li C. Hydrogen sulfide upregulates renal AQP-2 protein expression and promotes urine concentration. FASEB J. In press 2018
- Pan X, Shao Y, Wu F, Wang Y, Xiong R, Zheng J, Tian H, Wang B, Wang Y, Zhang Y, Han Z, Qu A, Xu H, Lu A, Yang T, Li X, Xu A, Du J, Lin Z. FGF21 Prevents Angiotensin II-Induced Hypertension and Vascular Dysfunction by Activation of ACE2/Angiotensin-(1-7) Axis in Mice. Cell Metab. 2018. pii: S1550-4131(18)30243-2
- Su J, Liu X, Xu C, Lu X, Wang F, Lu A, Fang H, Qiu Q, Li C, and Yang T. NF-κB-Dependent Upregulation of (Pro)Renin Receptor Mediates High NaCl-Induced Apoptosis in Mouse Inner Medullary Collecting Duct Cells. AJP-Cell Physiol In press 2017
- Fang H, Xu C, Lu A, Zou CJ, Xie S, Chen Y, Zhou L, Liu M, Wang L, Wang W, and Yang T. (Pro) renin receptor mediates albumin induced cellular responses: Role of site-1 protease-derived soluble (pro) renin receptor in renal epithelial cells. Am J Physiol-Cell Physiol. 313(6) 2017 C632-C643 doi: 10.1152/ajpcell.00006.
- Yang KT, Wang F, Lu X, Peng K, Yang T*, and Symons JD. The Soluble (Pro)Renin Receptor Does Not Influence Lithium-Induced Diabetes Insipidus but Does Provoke Beiging of White Adipose Tissue in Mice. Physiol Rep. Nov;5(21):e13410. doi: 10.14814/phy2.13410, 2017 (*parallel senior author)
- Liu M, Su J, Jia Z, Sun Y, Peng K, Deng M, Wang F, and Yang T. Specific Down-regulation of Cystathionine β-synthase Expression in the Kidney during Obesity. Physiol Rep. In press 2017
- Ramkumar N, Stuart D, Yang T, Kohan DE. Aldosterone does not alter endothelin B receptor signaling in the inner medullary collecting duct. Physiol Rep. 2017 Mar;5(5). pii: e13167. doi: 10.14814/phy2.13167
- Wang L, Zhu Q, Lu A, Liu X, Zhang L, Xu C, Liu X, Li H, Yang T. Sodium butyrate suppresses angiotensin II-induced hypertension by inhibition of renal (pro)renin receptor and intrarenal RAS. J Hyperten 2017 May 13. doi: 10.1097/HJH.0000000000001378.
- Xu C, Lu A, Fang H, Zhou L, and Yang T. Activation of Renal (Pro)Renin Receptor Contributes to High Fuctose-Induced Salt Sensitivity. Hypertension69:339-348, 2017
- Luo R, Kakizoe Y, Wang F, Fan X, Hu S, Yang T, Wang W, and Li C. Deficiency of mPGES-1 exacerbates renal fibrosis and inflammation in mice with unilateral ureteral obstruction. AJP-Renal 312(1):F121-F133, 2017
- Xu C, Fang H, Zhou L, Lu A, and Yang T. High potassium promotes mutual interaction between (pro)renin receptor and the local renin-angiotensin-aldosterone system in rat IMCD cells. AJP-Cell Physiology. 311:C686-C695 2016
- Song K, Stuart D, Abraham N, Wang F, Wang S, Yang T, Sigmund CD, Kohan DE, Ramkumar N.Ramkumar N. Collectingductrenin does not mediate DOCA-salt hypertension or renalinjury. PLoS One. 11(7):e0159872, 2016
- Xu C, Lu A, Wang H, Fang H, Zhou L, Sun P, and Yang T. (Pro)renin receptor regulates potassium homeostasis through a local mechanism. Am J Physiol-Renal Physiol.2016 Jul 20:ajprenal.00043.
- Peng K, Lu X, Wang F, Nau A, Chen R, Zhou S-F, and Yang T. Collecting duct (pro)renin receptor targets ENaC to mediate angiotensin II-induced hypertension. AJP-Renal 312(2):F245-F253, 2017
- Lu X, Wang F, Xu C, Soodvilai S, Peng K, Su J, Zhao L, Yang KT, Feng Y, Zhou S-F, Gustafsson JA, and Yang T. Soluble (Pro)renin receptor via β-catenin enhances urine concentration capability: A target of liver X receptor. Proc Natl Acad Sci USA 113:E1898-906, 2016
- Wang F, Lu X, Peng K, Xu C, Yang K, Zhou L, Feng Y, Ichihara A, Lu A, and Yang T. Antidiuretic action of collecting duct (pro)renin receptor and its interaction with vasopressin/the EP4 receptor. J Am Soc Nephrol. 27:3022-3034, 2016
- Wang W, Luo R, Lin Y, Wang F, Zheng P, Levi M, Yang T, Li C. Aliskiren restores renal AQP2 expression during unilateral ureteral obstruction by inhibiting the inflammasome. Am J Physiol-Renal Physiol. 2015 Apr 15;308(8):F910-22. doi: 10.1152/ajprenal.00649.2014. Epub 2015 Feb 18. PubMed PMID: 25694485.
- Li C, Lin Y, Luo R, Chen S, Wang F, Zheng P, Levi M, Yang T, and Wang W. Intrarenal renin-angiotensin system mediates fatty acid-induced ER stress in the kidney. Am J Physiol-Renal Physiol.310(5):F351-63, 2016
- Lu X, Wang F, Liu M, Yang KT, Nau A, Kohan DE, Reese VR, Richarson RS, and Yang T. Activation of ENaC in collecting duct cells by prorenin and its receptor PRR: Involvement of Nox4-derived hydrogen peroxide. Am J Physiol-Renal Physiol. 1;310:F1243-50, 2016
- Wang F, Lu X, Liu M, Feng Y, Zhou SF, Yang T. Renal medullary (pro)rennin receptor contributes to angiotensin II-induced hypertension in rats via activation of the local renin-angiotensin system. BMC Med. 13:278. 2015 Nov 10;doi: 10.1186/s12916-015-0514-1. PubMed PMID: 26554902; PubMed Central PMCID:PMC4641338
Review and editorial articles
- Yang T. Targeting angiotensin AT2 receptors in renal disease. Am J Physiol-Renal Physiology In press 2021
- Xu CM, Yang T. New advances in renal mechanisms of high fructose-induced salt-sensitive hypertension. Acta Physiologica Sinica, December 25, 70(6): 581–590, 2018
- Yang K, Yang T, and JD Symons. Soluble (pro)renin receptor as a potential therapy for diabetes insipidus. Am J Physiol-Renal Physiology 315:F1416-F1421, 2018
- Zhu Q, Yang T. Enzymatic sources and physio-pathological functions of soluble (pro)renin receptor. Current Opinion in Nephrology and Hypertension. In press 2018
- Yang T. Lewis K. Dahl Memorial Lecture: Unraveling the physiology of (pro)renin receptor in the distal nephron. Hypertension. 69:564-574, 2017
- Yang T and Xu C. The physiology and pathophysiology of intrarenal renin-angiotensin system: an update. JASN 28:1040-1049, 2017
- Yang T and Liu M. Regulation and function of renal medullary cyclooxygenase-2 during high salt loading. Front Biosci (Landmark Ed). 22:128-136, 2017
- Wang W, Li C, and Yang T. Protection of nitro-fatty acid against kidney diseases. AJP-Renal. In press 2015
- Yang T and Li C. Role of COX-2 in unilateral ureteral obstruction: What is new? AJP-Renal In press 2015
- Yang T. Crosstalk between (pro)renin receptor and COX-2 in the renal medulla during angiotensin II-induced hypertension. Current Opinion in Pharmacology Apr;21;89-94, 2015
- Yang T and Du Y. Distinct roles of central and peripheral PGE2 in blood pressure regulation. Am J Hyperten (State of the art) . 25:1042-9, 2012
- Yang T. Prostaglandin E2 and blood pressure regulation. Current Hypertension Review. In press 2010
- Yang T and Soodvilai S. Mechanisms of thiazolidinedione-induced fluid retention. PPAR Research. 2008;2008:943614
- Yang T. Kidney-specific gene targeting: Insights into thiazolidinedione-induced fluid retention. Nephrology (Carlton). 21:583-91, 2006
- Yang T. Regulation of cyclooxygenase-2 in renal medulla. Acta Physiologica Scandinavica 177:417-421, 2003
- Schnermann J, Traynor T, Yang T, Arend L, Huang Y, Smart A, Briggs JP. Tubuloglomerular feedback: New concepts and developments. Kidney Int 54(67), S40-S45, 1998