Uromodulin is expressed in the distal convoluted tubule, where it is critical for regulation of the sodium chloride cotransporter NCC

Kidney International
Natsuko TokonamiEric G Olinger

Abstract

Uromodulin, the most abundant protein in normal urine, is essentially produced by the cells lining the thick ascending limb. There it regulates the activity of the cotransporter NKCC2 and is involved in sodium chloride handling and blood pressure regulation. Conflicting reports suggested that uromodulin may also be expressed in the distal convoluted tubule (DCT) where its role remains unknown. Using microdissection studies combined with fluorescent in situ hybridization and co-immunostaining analyses, we found a significant expression of uromodulin in mouse and human DCT at approximately 10% of thick ascending limb expression levels, but restricted to the early part of the DCT (DCT1). Genetic deletion of Umod in mouse was reflected by a major shift in NCC activity from the DCT1 to the downstream DCT2 segment, paralleled by a compensatory expansion of DCT2. By increasing the distal sodium chloride and calcium ion load with chronic furosemide administration, an intrinsic compensatory defect in the DCT from Umod-/- compared to wild type mice was found manifested as sodium wasting and hypercalciuria. In line, co-expression studies in HEK cells suggested a facilitating role for uromodulin in NCC phosphorylation, possibly via SPAK-OS...Continue Reading

Citations

Jun 6, 2019·American Journal of Physiology. Renal Physiology·Marianela G DalghiGerard Apodaca
Jun 18, 2019·Current Opinion in Nephrology and Hypertension·Matthias T F WolfMingzhu Nie
Dec 17, 2019·American Journal of Physiology. Renal Physiology·Lise BankirPascal Houillier
Dec 4, 2019·Physiological Reviews·Ewout J HoornRobert A Fenton
Sep 7, 2019·Nature Reviews. Disease Primers·Olivier DevuystAnthony J Bleyer
May 9, 2019·International Journal of Nephrology·Nolubabalo Unati NqebeleleSaraladevi Naicker
Feb 23, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Christina M Coleman, Daneel Ferreira
Jan 17, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Radmila MicanovicTarek M El-Achkar
Jul 17, 2020·Nature·UNKNOWN Tabula Muris Consortium
Mar 7, 2020·Clinical Journal of the American Society of Nephrology : CJASN·Elisa Molinari, John A Sayer
Jul 14, 2020·American Journal of Physiology. Renal Physiology·Ryan J CorneliusJames A McCormick
Aug 26, 2020·Clinical Journal of the American Society of Nephrology : CJASN·Anne Kipp, Eric Olinger
Dec 22, 2019·Scientific Reports·Guglielmo SchianoOlivier Devuyst
Oct 14, 2020·Clinical Chemistry and Laboratory Medicine : CCLM·Dietmar EnkoSabine Zitta
Nov 3, 2020·American Journal of Physiology. Renal Physiology·Yujiro Maeoka, James A McCormick
Oct 30, 2020·Journal of the American Society of Nephrology : JASN·Valeria Rudman-MelnickS Steven Potter
Feb 11, 2021·Annual Review of Physiology·Céline SchaefferLuca Rampoldi
Mar 3, 2021·Journal of Proteome Research·Haiying LiRichard S Lee
Mar 9, 2021·Seminars in Nephrology·Christopher EstiverneDavid B Mount
Mar 9, 2021·Seminars in Nephrology·Megan P LeaskTony R Merriman
Mar 27, 2021·Journal of the American Society of Nephrology : JASN·Lihe ChenMark A Knepper
Mar 27, 2021·Journal of the American Society of Nephrology : JASN·Lihe ChenMark A Knepper
May 13, 2021·American Journal of Physiology. Cell Physiology·Helle Praetorius
May 23, 2021·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Anthony J BleyerStanislav Kmoch
Jul 27, 2021·KI Reports·Ngoentra TantranontLuan D Truong
Aug 14, 2020·Kidney International·Alexis WerionUNKNOWN Cliniques universitaires Saint-Luc (CUSL) COVID-19 Research Group
May 29, 2021·Journal of the American Society of Nephrology : JASN·David H EllisonJames A McCormick
Sep 21, 2021·Frontiers in Cardiovascular Medicine·Ruilian YouLimeng Chen
Sep 28, 2021·Frontiers in Medicine·Babak YazdaniMarcus E Kleber
Oct 12, 2021·American Journal of Physiology. Renal Physiology·Shivangi AgarwalMehmet M Altintas
Oct 21, 2021·Journal of the American Society of Nephrology : JASN·Chao GaoWenzheng Zhang
Sep 3, 2020·Acta Pharmaceutica Sinica. B·Vincent BlayDouglas R Houston

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