2023
High dietary K+ intake inhibits proximal tubule transport
Wang T, Liu T, Xu S, Frindt G, Weinstein A, Palmer L. High dietary K+ intake inhibits proximal tubule transport. American Journal Of Physiology. Renal Physiology 2023, 325: f224-f234. PMID: 37318989, PMCID: PMC10396284, DOI: 10.1152/ajprenal.00013.2023.Peer-Reviewed Original ResearchConceptsGlomerular filtration rateFree-flow micropunctureUrine volumeFractional excretion of Na<sup>+</sup>Proximal tubulesFiltration rateFractional NaNephron segmentsExcretion of Na<sup>+</sup>Dietary K<sup>+</sup>NHE3 protein expressionExchanger isoform 3Increased urine volumeIncreased fractional excretionVolume reabsorptionAbsolute NaKidney functionProtein expressionIsoform 3PT transportAnesthetized animalsReabsorptionWestern blottingRatsExcretion
2022
Regulation of glomerulotubular balance. IV. Implication of aquaporin 1 in flow-dependent proximal tubule transport and cell volume
Du Z, Yan Q, Shen E, Weinstein A, Wang T. Regulation of glomerulotubular balance. IV. Implication of aquaporin 1 in flow-dependent proximal tubule transport and cell volume. American Journal Of Physiology. Renal Physiology 2022, 323: f642-f653. PMID: 36108052, PMCID: PMC9705020, DOI: 10.1152/ajprenal.00167.2022.Peer-Reviewed Original ResearchConceptsWater channel aquaporin-1Proximal tubulesKO miceAquaporin-1Water reabsorptionMouse PTNo significant differenceWild-typeTight junctionsRat kidneyAquaporin-1 knockoutSignificant differenceAcid-base parametersKidney proximal tubulesRenal clearance experimentsWT miceKnockout miceUrine flowFlow stimulationFluid absorptionUrine pHClearance experimentsMouse kidneyMiceRats
2021
Sex difference in kidney electrolyte transport III: Impact of low K intake on thiazide-sensitive cation excretion in male and female mice
Xu S, Li J, Yang L, Wang CJ, Liu T, Weinstein AM, Palmer LG, Wang T. Sex difference in kidney electrolyte transport III: Impact of low K intake on thiazide-sensitive cation excretion in male and female mice. Pflügers Archiv - European Journal Of Physiology 2021, 473: 1749-1760. PMID: 34455480, PMCID: PMC8528772, DOI: 10.1007/s00424-021-02611-5.Peer-Reviewed Original ResearchConceptsGlomerular filtration rateFemale miceUrine volumeNaCl cotransporterLow K intakeMeasurement of functionSex differencesNatriuretic responseFractional excretionK intakeTransport protein expressionFiltration rateNCC abundanceNCC expressionRenal clearanceDistal nephronLK dietCation excretionPlasma KNCC proteinNKCC2 expressionWestern blottingProtein expressionMiceFENaRestoration of proximal tubule flow-activated transport prevents cyst growth in polycystic kidney disease
Du Z, Tian X, Ma M, Somlo S, Weinstein AM, Wang T. Restoration of proximal tubule flow-activated transport prevents cyst growth in polycystic kidney disease. JCI Insight 2021, 6: e146041. PMID: 33886508, PMCID: PMC8262298, DOI: 10.1172/jci.insight.146041.Peer-Reviewed Original ResearchConceptsGlomerular filtration rateGlomerulotubular balanceRenal cyst formationCyst formationReceptor 1 antagonistPolycystic kidney diseaseKidney weightUntreated miceDA1 antagonistControl miceKidney diseaseFiltration rateFractional reabsorptionCystic indexMouse modelCyst growthConditional KOHCO3- absorptionHeterozygous miceSame antagonistsMicePT transportAntagonistEpithelial ciliaHCO3- transportDeletion of Cdh16 Ksp-cadherin leads to a developmental delay in the ability to maximally concentrate urine in mouse
Thomson R, Dynia DW, Burlein S, Thomson BR, Booth C, Knauf F, Wang T, Aronson P. Deletion of Cdh16 Ksp-cadherin leads to a developmental delay in the ability to maximally concentrate urine in mouse. American Journal Of Physiology. Renal Physiology 2021, 320: f1106-f1122. PMID: 33938239, PMCID: PMC8285649, DOI: 10.1152/ajprenal.00556.2020.Peer-Reviewed Original ResearchConceptsKsp-cadherinCell adhesion moleculeAtypical memberKidney developmentMammalian kidneyAdult mammalian kidneyBasolateral membraneNormal kidney developmentEpithelial cellsAdhesion moleculesMutant animalsExpression analysisSpecific expressionE-cadherin expressionWestern blot analysisEpithelial phenotypePrincipal proteinE-cadherinBlot analysisMouse linesAquaporin-2CadherinCritical roleDevelopmental delayKnockout mice
2019
Sex difference in kidney electrolyte transport II: impact of K+ intake on thiazide-sensitive cation excretion in male and female mice
Li J, Xu S, Yang L, Yang J, Wang CJ, Weinstein AM, Palmer LG, Wang T. Sex difference in kidney electrolyte transport II: impact of K+ intake on thiazide-sensitive cation excretion in male and female mice. American Journal Of Physiology. Renal Physiology 2019, 317: f967-f977. PMID: 31390232, PMCID: PMC6843050, DOI: 10.1152/ajprenal.00125.2019.Peer-Reviewed Original ResearchConceptsHK dietCation excretionWT animalsFemale animalsMale animalsSex differencesRenal clearance experimentsGlomerular filtration rateR KO miceExchanger isoform 3Distal NaHK intakeWestern blot analysisFractional excretionUrine volumeFiltration rateFemale miceKO miceNHE3 abundanceClearance experimentsNCC abundanceLittle sex differenceKnockout miceENaC expressionExcretion
2018
Potassium conservation is impaired in mice with reduced renal expression of Kir4.1
Malik S, Lambert E, Zhang J, Wang T, Clark H, Cypress M, Goldman B, Porter GA, Pena S, Nino W, Gray D. Potassium conservation is impaired in mice with reduced renal expression of Kir4.1. American Journal Of Physiology. Renal Physiology 2018, 315: f1271-f1282. PMID: 30110571, PMCID: PMC6293297, DOI: 10.1152/ajprenal.00022.2018.Peer-Reviewed Original ResearchMeSH KeywordsAlkalosisAnimalsAquaporin 3Gene Knockdown TechniquesGenotypeHypercalcemiaHyperkalemiaHypernatremiaKidney Concentrating AbilityMice, Inbred C57BLMice, KnockoutNephronsPhenotypePhosphorylationPotassium Channels, Inwardly RectifyingPotassium, DietaryRenal ReabsorptionSolute Carrier Family 12, Member 3ConceptsMg-free dietSevere urinary concentrating defectReduced renal expressionRenal K wastingSeSAME/EAST syndromeDistal convoluted tubuleKir4.1 protein expressionWild-type miceUrinary concentrating defectCre-LoxP methodologyAquaporin 3 expressionRelative hypercalcemiaRenal expressionPotassium conservationMetabolic alkalosisNCC expressionChannel Kir4.1Distal nephronKnockout miceConvoluted tubulesCotransporter expressionEAST syndromeHypokalemiaMiceReduced expressionRegulation of renal Na transporters in response to dietary K
Yang L, Xu S, Guo X, Uchida S, Weinstein AM, Wang T, Palmer LG. Regulation of renal Na transporters in response to dietary K. American Journal Of Physiology. Renal Physiology 2018, 315: f1032-f1041. PMID: 29923764, PMCID: PMC6230734, DOI: 10.1152/ajprenal.00117.2018.Peer-Reviewed Original Research
2017
Urinary bladder hypertrophy characteristic of male ROMK Bartter’s mice does not occur in female mice
Kim JM, Xu S, Guo X, Hu H, Dong K, Wang T. Urinary bladder hypertrophy characteristic of male ROMK Bartter’s mice does not occur in female mice. AJP Regulatory Integrative And Comparative Physiology 2017, 314: r334-r341. PMID: 29092859, PMCID: PMC5899254, DOI: 10.1152/ajpregu.00315.2017.Peer-Reviewed Original ResearchConceptsKO miceBladder hypertrophyBladder weightUrinary bladder hypertrophyRenal outer medullary potassium channelSeverity of hydronephrosisWild-type miceROMK knockout miceBladder capacityDetrusor muscleWT miceUrinary tractBartter's syndromeFemale miceSalt wastingHydronephrosisKnockout miceROMK expressionMiceBladderHypertrophyPotassium channelsMRNA levelsSignificant enlargementSyndromeGender difference in kidney electrolyte transport. I. Role of AT1a receptor in thiazide-sensitive Na+-Cl− cotransporter activity and expression in male and female mice
Li J, Hatano R, Xu S, Wan L, Yang L, Weinstein AM, Palmer L, Wang T. Gender difference in kidney electrolyte transport. I. Role of AT1a receptor in thiazide-sensitive Na+-Cl− cotransporter activity and expression in male and female mice. American Journal Of Physiology. Renal Physiology 2017, 313: f505-f513. PMID: 28566500, PMCID: PMC5582908, DOI: 10.1152/ajprenal.00087.2017.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAnimalsDiuresisFemaleHydrochlorothiazideKidneyMaleMice, KnockoutNatriuresisPhenotypeProtein Serine-Threonine KinasesReceptor, Angiotensin, Type 1Receptors, DrugSex CharacteristicsSodium Chloride SymportersSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSolute Carrier Family 12, Member 3ConceptsUrine volumeKO miceCotransporter activityRenal clearance experimentsReceptor knockout miceGlomerular filtration rateBolus intravenous injectionDelivery of NaClNCC protein expressionGender differencesFiltration rateFemale miceAT1A receptorClearance experimentsKO animalsIntravenous injectionNCC expressionDistal nephronFractional NaKnockout miceMale KOProximal tubulesHCTZMiceNHE3 expressionRegulation of glomerulotubular balance: flow-activated proximal tubule function
Wang T, Weinbaum S, Weinstein A. Regulation of glomerulotubular balance: flow-activated proximal tubule function. Pflügers Archiv - European Journal Of Physiology 2017, 469: 643-654. PMID: 28271233, PMCID: PMC6162058, DOI: 10.1007/s00424-017-1960-8.Peer-Reviewed Original ResearchConceptsNa/H exchanger isoform 3Proximal tubulesTubule functionIntracellular Ca2+ signalingProximal tubule transportMammalian proximal tubuleAcid-base transportersProximal tubule functionRegulation of sodiumCa2+ signalingHCO3- absorptionStimulate Na+Tubule transportMicropuncture studiesSolute reabsorptionPeritubular membraneBrush border membraneBrush border microvilliGlomerulotubular balanceHCO3- transportIsoform 3Flow velocity changesTubulesRegulatory mechanismsTransporter availability
2016
Kidney Tubular Ablation of Ocrl/Inpp5b Phenocopies Lowe Syndrome Tubulopathy
Inoue K, Balkin DM, Liu L, Nandez R, Wu Y, Tian X, Wang T, Nussbaum R, De Camilli P, Ishibe S. Kidney Tubular Ablation of Ocrl/Inpp5b Phenocopies Lowe Syndrome Tubulopathy. Journal Of The American Society Of Nephrology 2016, 28: 1399-1407. PMID: 27895154, PMCID: PMC5407733, DOI: 10.1681/asn.2016080913.Peer-Reviewed Original ResearchConceptsEarly embryonic lethalityTransporter 5Dent's diseaseIndependent endocytosisEmbryonic lethalityRedundant functionsType 2 inositolHuman phenotypesProximal tubule endocytosisOculocerebrorenal syndromeGenetic ablationCellular levelGermline knockoutLowe syndromeEndocytosisMouse backgroundMice resultsMutationsInositolLow molecular weight proteinuriaINPP5BParalogsProximal tubule functionDramatic effectOCRLPotassium Channelopathies and Gastrointestinal Ulceration
Han J, Lee SH, Giebisch G, Wang T. Potassium Channelopathies and Gastrointestinal Ulceration. Gut And Liver 2016, 10: 881-889. PMID: 27784845, PMCID: PMC5087926, DOI: 10.5009/gnl15414.Peer-Reviewed Original ResearchConceptsPotassium channelsGI tractPotassium channelopathiesAdenosine triphosphate-sensitive potassium channel openerTriphosphate-sensitive potassium channel openerNonsteroidal anti-inflammatory drugsAntianginal drug nicorandilAnti-inflammatory drugsPotassium channel openersOccurrence of ulcerationPotassium channel activityLong-term useRegulation of secretionGastrointestinal ulcerationUlcerative colitisPeptic ulcerationChannel openersGastric acidGastrointestinal tractUlcerationDifferent biological actionsTransporter inhibitorsAnal regionPotassium homeostasisTract
2015
Regulation of glomerulotubular balance. III. Implication of cytosolic calcium in flow-dependent proximal tubule transport
Du Z, Weinbaum S, Weinstein A, Wang T. Regulation of glomerulotubular balance. III. Implication of cytosolic calcium in flow-dependent proximal tubule transport. American Journal Of Physiology. Renal Physiology 2015, 308: f839-f847. PMID: 25651568, PMCID: PMC4398834, DOI: 10.1152/ajprenal.00601.2014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBicarbonatesBiological TransportCalciumCalcium-Transporting ATPasesChelating AgentsCytosolEnzyme InhibitorsIn Vitro TechniquesInositol 1,4,5-Trisphosphate ReceptorsKidney Tubules, ProximalKineticsMice, Inbred C57BLPerfusionRenal ReabsorptionSodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersConceptsNa/H exchanger 3Luminal Ca(2Flow-induced increaseCytosolic calciumProximal tubulesCa(2+) chelator BAPTA-AMAntagonist 2-aminoethoxydiphenyl borateCa-ATPase inhibitor thapsigarginProximal tubule transportNa(+) reabsorptionMicroperfused in vitroMouse proximal tubuleChelator BAPTA-AMH-ATPase activityNo effectControl tubulesInhibitor thapsigarginBAPTA-AMIntracellular Ca(2Decreased transportTubule transportBaseline transportStimulates Na(+Modulate Na(+Glomerulotubular balance
2014
Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1
Vucic E, Alfadda T, MacGregor GG, Dong K, Wang T, Geibel JP. Kir1.1 (ROMK) and Kv7.1 (KCNQ1/KvLQT1) are essential for normal gastric acid secretion: importance of functional Kir1.1. Pflügers Archiv - European Journal Of Physiology 2014, 467: 1457-1468. PMID: 25127675, DOI: 10.1007/s00424-014-1593-0.Peer-Reviewed Original ResearchConceptsGastric parietal cellsPotassium channelsParietal cellsΒ-subunitKir1.1 channelsWild-type miceSecretagogue-stimulated gastric acid secretionApical poleGastric glandsLeak pathwayPotential therapeutic targetKir1.1Proton secretionRegulatory characteristicsKv7.1Therapeutic targetATPaseCell numberParietal cell numberCellsNormal gastric acid secretionSecretionInhibitorsAcid secretionMice
2013
Proximal tubule specific knockout of the Na+/H+ exchanger NHE3: effects on bicarbonate absorption and ammonium excretion
Li H, Du Z, Barone S, Rubera I, McDonough A, Tauc M, Zahedi K, Wang T, Soleimani M. Proximal tubule specific knockout of the Na+/H+ exchanger NHE3: effects on bicarbonate absorption and ammonium excretion. Journal Of Molecular Medicine 2013, 91: 951-963. PMID: 23508938, PMCID: PMC3730089, DOI: 10.1007/s00109-013-1015-3.Peer-Reviewed Original ResearchConceptsNa+/H+ exchanger NHE3Proximal convoluted tubulesKO miceMetabolic acidosisBicarbonate reabsorptionDays of acid loadingIsolated proximal convoluted tubulesConvoluted tubulesIn vitro microperfusion studyCompared to WT miceNHE3 knockout miceProximal tubule NHE3Acid loadNH4Cl acid loadMild metabolic acidosisWT miceNHE3Microperfusion studiesKnockout miceBicarbonate absorptionMutant miceVolume reabsorptionFloxed miceNH4Cl loadingTransgenic miceOlfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation
Pluznick JL, Protzko RJ, Gevorgyan H, Peterlin Z, Sipos A, Han J, Brunet I, Wan LX, Rey F, Wang T, Firestein SJ, Yanagisawa M, Gordon JI, Eichmann A, Peti-Peterdi J, Caplan MJ. Olfactory receptor responding to gut microbiota-derived signals plays a role in renin secretion and blood pressure regulation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 4410-4415. PMID: 23401498, PMCID: PMC3600440, DOI: 10.1073/pnas.1215927110.Peer-Reviewed Original ResearchConceptsShort-chain fatty acidsRenin secretionBlood pressureGut microbiotaG protein-coupled receptor 41Acute hypotensive responseRenal juxtaglomerular apparatusSmall resistance vesselsMicrobiota-derived signalsModulate blood pressureBlood pressure regulationWild-type miceSmooth muscle cellsG protein-coupled receptorsGPR41 expressionOlfactory receptorsHypotensive responseProtein-coupled receptorsSCFA receptorsResistance vesselsJuxtaglomerular apparatusAntibiotic treatmentOlfr78Receptor 41Knockout mice
2012
Regulation of glomerulotubular balance. II. Impact of angiotensin II on flow-dependent transport
Du Z, Wan L, Yan Q, Weinbaum S, Weinstein A, Wang T. Regulation of glomerulotubular balance. II. Impact of angiotensin II on flow-dependent transport. American Journal Of Physiology. Renal Physiology 2012, 303: f1507-f1516. PMID: 22952281, PMCID: PMC3532483, DOI: 10.1152/ajprenal.00277.2012.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin IIAngiotensin II Type 1 Receptor BlockersAnimalsBicarbonatesBiological TransportEnzyme InhibitorsFemaleHemostasisIn Vitro TechniquesKidney GlomerulusKidney TubulesLosartanMacrolidesMiceMice, KnockoutModels, AnimalProton-Translocating ATPasesReceptor, Angiotensin, Type 1SodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersConceptsNa(+)-H(+) exchanger 3Mouse tubulesImpact of angiotensin IIH-ATPaseMicroperfused in vitroAT(2) receptorsAT(1A) receptorFlow-mediated changesH-ATPase activityParacellular Cl(-Receptor availabilityAngiotensin IIAT(1ARegulate Na(+Increased Na(+Local angiotensinBasolateral transportJ(HCO3Mouse kidneyNet fluidInhibitor bafilomycinProtein levelsMiceReceptorsTubulesGenetic modifiers of hypertension in soluble guanylate cyclase α1–deficient mice
Buys E, Raher M, Kirby A, Mohd S, Baron D, Hayton S, Tainsh L, Sips P, Rauwerdink K, Yan Q, Tainsh R, Shakartzi H, Stevens C, Decaluwé K, da Gloria Rodrigues-Machado M, Malhotra R, Van de Voorde J, Wang T, Brouckaert P, Daly M, Bloch K. Genetic modifiers of hypertension in soluble guanylate cyclase α1–deficient mice. Journal Of Clinical Investigation 2012, 122: 2316-2325. PMID: 22565307, PMCID: PMC3366402, DOI: 10.1172/jci60119.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCyclic GMPEndothelium, VascularFemaleGenetic LinkageGenome, HumanGuanylate CyclaseHumansHypertensionMaleMiceMice, KnockoutQuantitative Trait LociRatsReceptors, Cytoplasmic and NuclearReninRenin-Angiotensin SystemSecond Messenger SystemsSoluble Guanylyl CyclaseSpecies SpecificityVasodilationConceptsRenin-angiotensin-aldosterone systemRenin-angiotensin-aldosterone system inhibitionRelaxation of vascular smooth muscleVascular smooth muscleInducing relaxation of vascular smooth muscleNitric oxideEndothelium-dependent vasorelaxationSubunit of soluble guanylate cyclaseSoluble guanylate cyclaseImproving endothelium-dependent vasorelaxationSmooth muscleQuantitative trait lociArterial pressureMale miceMouse strainsNO/cGMP signalingInduced relaxationAssociated with increased activityHypertensionGuanylate cyclaseBlood flowMiceGenetic modifiersReceptor componentsGenetic factorsRegulation of glomerulotubular balance. I. Impact of dopamine on flow-dependent transport
Du Z, Yan Q, Wan L, Weinbaum S, Weinstein A, Wang T. Regulation of glomerulotubular balance. I. Impact of dopamine on flow-dependent transport. American Journal Of Physiology. Renal Physiology 2012, 303: f386-f395. PMID: 22552936, PMCID: PMC3433864, DOI: 10.1152/ajprenal.00531.2011.Peer-Reviewed Original ResearchMeSH Keywords8-Bromo Cyclic Adenosine MonophosphateAlgorithmsAnimalsBenzazepinesBicarbonatesBiological Transport, ActiveChloridesCyclic AMP-Dependent Protein KinasesDopamineDopamine AntagonistsDopamine D2 Receptor AntagonistsFemaleIsoquinolinesKidney GlomerulusKidney TubulesKidney Tubules, ProximalMacrolidesMiceMicrovilliProton-Translocating ATPasesReceptors, Dopamine D1SodiumSulfonamidesSulpirideConceptsNa/H exchanger 3Impact of dopamineNa(+) transportNa-K-ATPase activityResponse to volume expansionProximal tubules in vitroCl(-) reabsorptionPKA-mediated mechanismMicroperfused in vitroEffects of exogenous dopamineMouse proximal tubuleNa-K-ATPaseProximal tubule reabsorptionStimulation of Cl(-PKA inhibitor H89Luminal flowH-ATPase activityTubules in vitroLuminal flow rateNHE3 activityDA1 receptorsNa/H exchangeTubule reabsorptionProximal tubulesInhibitor H89