Mechanistic interactions of uromodulin with the thick ascending limb: perspectives in physiology and hypertension

Boder, P., Mary, S., Mark, P. B. , Leiper, J. , Dominiczak, A. F. , Padmanabhan, S. , Rampold, L. and Delles, C. (2021) Mechanistic interactions of uromodulin with the thick ascending limb: perspectives in physiology and hypertension. Journal of Hypertension, 39(8), pp. 1490-1504. (doi: 10.1097/HJH.0000000000002861) (PMID:34187999) (PMCID:PMC7611110)

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Abstract

Hypertension is a significant risk factor for cardiovascular disease and mortality worldwide. The kidney is a major regulator of blood pressure and electrolyte homeostasis, with monogenic disorders indicating a link between abnormal ion transport and salt-sensitive hypertension. However, the association between salt and hypertension remains controversial. Thus, there is continued interest in deciphering the molecular mechanisms behind these processes. Uromodulin (UMOD) is the most abundant protein in the normal urine and is primarily synthesized by the thick ascending limb epithelial cells of the kidney. Genome-wide association studies have linked common UMOD variants with kidney function, susceptibility to chronic kidney disease and hypertension independent of renal excretory function. This review will discuss and provide predictions on the role of the UMOD protein in renal ion transport and hypertension based on current observational, biochemical, genetic, pharmacological and clinical evidence.

Item Type:Articles
Additional Information:This work was supported by the British Heart Foundation 4-Year PhD Programme [FS/18/58/34179 to P.B.]; the British Heart Foundation [grant numbers RE/13/5/30177, RE/18/6/34217 to C.D. and J.L; BHF PG 128529925, BHF UMOD trial CS 16131878 to S.P.]; the Italian Society of Nephrology (SIN) under the “Adotta un progetto di ricerca” programme and by the Italian Ministry of Health [grant number RF 2016 02362623 to L.R.]; the Academy of Medical Sciences-Newton International fellowship [NIF 004\1010 to S.M.]; the Strength In Places Fund (SIPF) [grant number United Kingdom Research and Innovation 35049 to A.F.D]; the Medical Research Council [grant number AIM-HY Study MR M016560 1 to S.P.]; and the BHF Centre of Excellence [grant number RE 18 6 34217 to S.P.].
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Leiper, Professor James and Boder, Philipp and Mark, Professor Patrick and Padmanabhan, Professor Sandosh and Dominiczak, Professor Anna and Delles, Professor Christian
Authors: Boder, P., Mary, S., Mark, P. B., Leiper, J., Dominiczak, A. F., Padmanabhan, S., Rampold, L., and Delles, C.
College/School:College of Medical Veterinary and Life Sciences
College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Journal of Hypertension
Publisher:Wolters Kluwer Health
ISSN:0263-6352
ISSN (Online):1473-5598
Copyright Holders:Copyright © 2021 Wolters Kluwer Health, Inc.
First Published:First published in Journal of Hypertension 39(8):1490-1504
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
305659BHF 4-Year PhD Studentship Award 2018Rhian TouyzBritish Heart Foundation (BHF)FS/18/58/34179CAMS - Cardiovascular Science
190814BHF centre of excellenceRhian TouyzBritish Heart Foundation (BHF)RE/13/5/30177Institute of Cardiovascular & Medical Sciences
303944BHF Centre of ExcellenceRhian TouyzBritish Heart Foundation (BHF)RE/18/6/34217CAMS - Cardiovascular Science