Integrated compensatory network is activated in the absence of NCC phosphorylation.

The Journal of Clinical Investigation
P Richard GrimmPaul A Welling

Abstract

Thiazide diuretics are used to treat hypertension; however, compensatory processes in the kidney can limit antihypertensive responses to this class of drugs. Here, we evaluated compensatory pathways in SPAK kinase-deficient mice, which are unable to activate the thiazide-sensitive sodium chloride cotransporter NCC (encoded by Slc12a3). Global transcriptional profiling, combined with biochemical, cell biological, and physiological phenotyping, identified the gene expression signature of the response and revealed how it establishes an adaptive physiology. Salt reabsorption pathways were created by the coordinate induction of a multigene transport system, involving solute carriers (encoded by Slc26a4, Slc4a8, and Slc4a9), carbonic anhydrase isoforms, and V-type H⁺-ATPase subunits in pendrin-positive intercalated cells (PP-ICs) and ENaC subunits in principal cells (PCs). A distal nephron remodeling process and induction of jagged 1/NOTCH signaling, which expands the cortical connecting tubule with PCs and replaces acid-secreting α-ICs with PP-ICs, were partly responsible for the compensation. Salt reabsorption was also activated by induction of an α-ketoglutarate (α-KG) paracrine signaling system. Coordinate regulation of a multige...Continue Reading

References

Oct 1, 1976·The American Journal of Physiology·R L Tannen, J McGill
Aug 11, 1975·The Journal of Clinical Investigation·R T KunauH L Webb
Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·G Fejes-Tóth, A Náray-Fejes-Tóth
Feb 1, 1969·The Journal of Clinical Investigation·G A Alleyne, G H Scullard
Apr 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·Gerardo GambaSteven C Hebert
Oct 1, 1996·Kidney International·Johannes LoffingBrigitte Kaissling
Jan 20, 1999·Kidney International·N H GarcíaJeffrey L Garvin
Mar 29, 2001·Proceedings of the National Academy of Sciences of the United States of America·I E RoyauxEric D Green
Apr 9, 2001·American Journal of Physiology. Renal Physiology·Susan M WallS J Park
Aug 11, 2001·Science·F H WilsonRichard P Lifton
Aug 15, 2001·American Journal of Physiology. Renal Physiology·N P Curthoys, G Gstraunthaler
Dec 26, 2001·Nucleic Acids Research·Ron EdgarAlex E Lash
Sep 10, 2002·American Journal of Physiology. Renal Physiology·Young Hee KimSøren Nielsen
Oct 22, 2002·American Journal of Physiology. Renal Physiology·Susan M WallJill W Verlander
Nov 6, 2002·The Journal of Clinical Investigation·Peer WulffDietmar Kuhl
Dec 20, 2002·JAMA : the Journal of the American Medical Association·ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. The Antihypertensive and Lipid-Lowering Treatm
Sep 2, 2004·Journal of the American Society of Nephrology : JASN·Johannes LoffingBrigitte Kaissling
Jan 26, 2006·American Journal of Physiology. Renal Physiology·Ryan G MorrisM A Knepper
May 4, 2006·American Journal of Physiology. Renal Physiology·Jill W VerlanderSusan M Wall
Jul 4, 2006·Biochimica Et Biophysica Acta·Anusorn LungkaphinVaranuj Chatsudthipong
Jul 11, 2006·Journal of the American Society of Nephrology : JASN·Marion ValletDominique Eladari
Oct 25, 2006·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Eva Riveira-MunozOlivier Devuyst
Nov 28, 2006·Frontiers in Bioscience : a Journal and Virtual Library·John D McGivan, Claire I Bungard
Dec 23, 2006·Histochemistry and Cell Biology·Philipp WehrliJohannes Loffing
Apr 6, 2007·Journal of the American Society of Nephrology : JASN·Paul A StehbergerCarsten A Wagner
Aug 10, 2007·American Journal of Physiology. Renal Physiology·Young Hee KimSusan M Wall
Sep 15, 2007·Journal of the American Society of Nephrology : JASN·Hyun-Kuk SongJin Kim
Feb 14, 2008·Journal of Cell Science·Ciaran RichardsonDario R Alessi
Mar 14, 2008·Journal of the American Society of Nephrology : JASN·Soundarapandian VijayakumarQais Al-Awqati
Apr 16, 2008·The Journal of Biological Chemistry·Andrew BahnGerhard Burckhardt
Dec 31, 2008·Proceedings of the National Academy of Sciences of the United States of America·Ying WangYen-Pei C Chang
Jan 10, 2009·Nature Protocols·Da Wei HuangRichard A Lempicki
May 22, 2009·American Journal of Physiology. Renal Physiology·Stephanie M Busque, Carsten A Wagner
May 29, 2009·American Journal of Physiology. Renal Physiology·Gerardo Gamba
Jul 3, 2009·American Journal of Physiology. Renal Physiology·Volker VallonShinichi Uchida
Sep 26, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Anna CasselbrantLars Fändriks
Oct 27, 2009·The Journal of Clinical Investigation·Hyun-Woo JeongYoung-Yun Kong
Apr 9, 2010·Kidney International·Paul A WellingJames B Wade
Sep 4, 2010·Journal of the American Society of Nephrology : JASN·Sung-Sen YangShih-Hua Lin
Oct 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jianghui HouSiegfried Waldegger
Oct 23, 2010·Journal of the American Society of Nephrology : JASN·Vladimir PechSusan M Wall
Nov 18, 2010·Physiological Genomics·Lydie ChevalAlain Doucet
Nov 26, 2010·Proceedings of the National Academy of Sciences of the United States of America·Xiaobo GaoQais Al-Awqati
Jul 29, 2011·American Journal of Physiology. Renal Physiology·Shaikh Abu HossainHassane Amlal
Aug 26, 2011·American Journal of Physiology. Renal Physiology·Marcel KaufholdGerhard Burckhardt
Sep 13, 2011·Cell Metabolism·James A McCormickDavid H Ellison
Sep 17, 2011·American Journal of Physiology. Renal Physiology·Jill W VerlanderSusan M Wall
Nov 26, 2011·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Juliette HadchouelDominique Eladari
Jan 21, 2012·American Journal of Physiology. Renal Physiology·Anie AzroyanAlain Doucet
May 3, 2012·Pflügers Archiv : European journal of physiology·Nils van der LubbeEwout J Hoorn
May 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·María Castañeda-BuenoGerardo Gamba
Aug 1, 2012·Proceedings of the National Academy of Sciences of the United States of America·Manoocher SoleimaniHassane Amlal
Sep 15, 2012·The Journal of Biological Chemistry·P Richard GrimmPaul A Welling
Oct 18, 2012·Physiological Reviews·Kenneth B Gagnon, Eric Delpire
Apr 24, 2013·Proceedings of the National Academy of Sciences of the United States of America·Régine ChambreyDominique Eladari
Apr 27, 2013·The Journal of Clinical Investigation·Romer A Gonzalez-VillalobosAlicia A McDonough
May 3, 2013·American Journal of Physiology. Renal Physiology·Susan M Wall, Alan M Weinstein
May 21, 2013·FEBS Letters·Qais Al-Awqati
Jun 15, 2013·Journal of the American Society of Nephrology : JASN·Thibaut JacquesDominique Eladari
Jul 5, 2013·American Journal of Physiology. Renal Physiology·Francesco TrepiccioneBirgitte Mønster Christensen
Aug 13, 2013·The Journal of Clinical Investigation·Natsuko TokonamiDmitri Firsov
Aug 21, 2013·Seminars in Nephrology·L Lee HammNazih L Nakhoul
Sep 21, 2013·The Journal of Clinical Investigation·Victor GueutinRégine Chambrey
Oct 12, 2013·Pflügers Archiv : European journal of physiology·Ana M Pajor
Mar 25, 2014·Bioscience Reports·Daiei TakahashiShinichi Uchida
Apr 12, 2014·Current Opinion in Pharmacology·Bernard C Rossier
May 16, 2014·American Journal of Physiology. Renal Physiology·Glenn T NagamiOran Schachter

Citations

Dec 25, 2015·Expert Review of Proteomics·Francesca RaimondoMarina Pitto
Dec 15, 2015·Annual Review of Physiology·Paul A Welling
Feb 11, 2016·Annual Review of Physiology·Juliette HadchouelGerardo Gamba
Aug 12, 2015·Experimental Physiology·Crystal A WestChris Baylis
Apr 22, 2015·The Journal of Clinical Investigation·M A Knepper
May 7, 2016·Journal of the American Society of Nephrology : JASN·Anne SinningRégine Chambrey
May 20, 2016·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Aylin R Rodan
Dec 30, 2015·Journal of the American Society of Nephrology : JASN·Andrew S TerkerDavid H Ellison
Apr 14, 2016·The Journal of Physiology·Mohammed Z FerdausJames A McCormick
Nov 7, 2016·Cellular and Molecular Life Sciences : CMLS·Meena MurthyKevin M O'Shaughnessy
Apr 4, 2017·European Journal of Heart Failure·Doron Aronson
Dec 2, 2016·Current Opinion in Pediatrics·Hannsjörg W SeyberthMartin Kömhoff
Jun 1, 2017·Clinical Pharmacology and Therapeutics·C-J ChengC-L Huang
Apr 28, 2016·Physiological Reports·Gunars OsisI David Weiner
Dec 3, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Premraj RajkumarJennifer L Pluznick
Sep 24, 2017·The Journal of Physiology·Khalil UdwanEric Feraille
Dec 9, 2016·American Journal of Physiology. Renal Physiology·Hyun-Wook LeeI David Weiner
Mar 17, 2016·World Journal of Biological Chemistry·Luciana MorlaGilles Crambert
Feb 8, 2018·American Journal of Physiology. Renal Physiology·Yoskaly Lazo-FernandezSusan M Wall
Jul 22, 2018·Physiological Reports·Wouter H van MegenJenny van der Wijst
Nov 30, 2018·American Journal of Physiology. Renal Physiology·Bangchen WangSteven C Sansom
Mar 16, 2017·Journal of the American Society of Nephrology : JASN·Lama Al-QusairiO Staub
Apr 27, 2017·Journal of the American Society of Nephrology : JASN·P Richard GrimmPaul A Welling
Jul 4, 2019·Current Opinion in Nephrology and Hypertension·Aylin R Rodan
Oct 20, 2017·American Journal of Physiology. Renal Physiology·Crystal A WestMichelle L Gumz
Dec 17, 2019·American Journal of Physiology. Renal Physiology·Hyun-Wook LeeI David Weiner
Jan 31, 2020·Physiological Reviews·Jens Leipziger, Helle Praetorius
Apr 30, 2020·Physiological Reviews·Susan M WallCesar A Romero
Dec 4, 2019·Physiological Reviews·Ewout J HoornRobert A Fenton
Sep 8, 2020·American Journal of Physiology. Renal Physiology·Akira OnishiVolker Vallon
Dec 5, 2019·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·K Mutig, S Bachmann
Nov 16, 2017·The New England Journal of Medicine·David H Ellison, G Michael Felker
Nov 7, 2019·Biomolecules·Malini MukherjeeKameswaran Surendran
Jan 31, 2020·Journal of the American Society of Nephrology : JASN·Dominique M BovéeEwout J Hoorn
Nov 6, 2015·American Journal of Physiology. Renal Physiology·Susan M Wall
Apr 15, 2016·American Journal of Physiology. Renal Physiology·Mohammed Z Ferdaus, James A McCormick
Aug 5, 2017·Current Opinion in Nephrology and Hypertension·P Richard Grimm, Paul A Welling
Mar 1, 2019·Nature Reviews. Molecular Cell Biology·Markus M RinschenGary Siuzdak
Aug 28, 2020·Experimental Animals·Daniel Mota-RojasAgustín Orihuela
Apr 14, 2020·American Journal of Physiology. Renal Physiology·Cary R Boyd-ShiwarskiArohan R Subramanya
Jul 1, 2020·Acta Physiologica·Gijs A C FrankenJeroen H F de Baaij
Jan 5, 2021·Clinical Kidney Journal·Kuang-Yu WeiEwout J Hoorn
Aug 28, 2017·Kidney International·Jae Wook LeeCarolyn A Ecelbarger
Mar 14, 2020·Journal of the American College of Cardiology·G Michael FelkerJeffrey M Testani

Datasets Mentioned

BETA
GSE60728

Methods Mentioned

BETA
PCR
transcription profiling
glycosylation
confocal microscopy
deamination
genotyping
Assay
protein assay

Related Concepts

Benzamil
alpha-ketoglutaric acid, sodium salt
Stk39 protein, mouse
P2Y15 protein, mouse
Slc12a3 protein, mouse
Kaluril
Ammonia
Metazoa
Diastolic Blood Pressure
Carbonate Dehydratase

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