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 ResearchMeSH KeywordsAnimalsGlomerular Filtration RateKidneyKidney Tubules, ProximalNephronsRatsSodiumSodium-Hydrogen Exchanger 3ConceptsGlomerular 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
Restoration 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 ResearchMeSH KeywordsAnimalsBenzazepinesDisease Models, AnimalFemaleKidneyKidney Tubules, ProximalMaleMiceMice, KnockoutPolycystic Kidney DiseasesReceptors, Dopamine D1TRPP Cation ChannelsConceptsGlomerular 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- transport
2018
Regulation 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
Regulation 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 ResearchMeSH KeywordsAnimalsGlomerular Filtration RateHumansKidney Tubules, ProximalRenal ReabsorptionSodium-Hydrogen Exchanger 3Sodium-Potassium-Exchanging ATPaseConceptsNa/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 ResearchMeSH KeywordsAnimalsHumansKidney Tubules, ProximalMiceMice, KnockoutMutationOculocerebrorenal SyndromePhenotypePhosphoric Monoester HydrolasesConceptsEarly 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 effectOCRL
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
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 mice
2012
Regulation 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
2011
Chloride Channel (Clc)-5 Is Necessary for Exocytic Trafficking of Na+/H+ Exchanger 3 (NHE3)*
Lin Z, Jin S, Duan X, Wang T, Martini S, Hulamm P, Cha B, Hubbard A, Donowitz M, Guggino SE. Chloride Channel (Clc)-5 Is Necessary for Exocytic Trafficking of Na+/H+ Exchanger 3 (NHE3)*. Journal Of Biological Chemistry 2011, 286: 22833-22845. PMID: 21561868, PMCID: PMC3123051, DOI: 10.1074/jbc.m111.224998.Peer-Reviewed Original ResearchConceptsKO miceTrafficking of NHE3Proximal tubulesOpossum kidney cellsNHE3 activityDent's diseaseClC-5Surface expressionNHE3 surface expressionKidney cellsRenal proximal tubulesTotal protein levelsChloride/proton exchangerRates of basalReduced surface expressionKnockdown cellsParathyroid hormoneWT miceDegree of inhibitionCLCN5 geneSurface NHE3MiceTubule perfusionReduced expressionTwo-photon microscopy
2010
Shear stress-induced changes of membrane transporter localization and expression in mouse proximal tubule cells
Duan Y, Weinstein A, Weinbaum S, Wang T. Shear stress-induced changes of membrane transporter localization and expression in mouse proximal tubule cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 21860-21865. PMID: 21106755, PMCID: PMC3003103, DOI: 10.1073/pnas.1015751107.Peer-Reviewed Original ResearchConceptsProximal tubule cellsMouse proximal tubuleNa/K-ATPaseTubule cellsApical NHE3Proximal tubulesMouse proximal tubule cellsFSS-induced changesApical plasma membraneV-ATPaseAmount of protein expressionBasolateral membraneWestern blot analysisNHE3Volume reabsorptionTransporter expressionBasolateral transportProtein expressionMPT cellsShear stress-induced changesVacuolar H(+)-ATPaseBlock microtubule polymerizationControl cellsModulate cellular functionsTransporter localizationMechanotransduction in the renal tubule
Weinbaum S, Duan Y, Satlin L, Wang T, Weinstein A. Mechanotransduction in the renal tubule. American Journal Of Physiology. Renal Physiology 2010, 299: f1220-f1236. PMID: 20810611, PMCID: PMC3006307, DOI: 10.1152/ajprenal.00453.2010.Peer-Reviewed Original ResearchConceptsCortical collecting ductCa(2+) signalingProximal tubulesModulation of Na(+Stretch-activated ion channelsDistal nephronRenal epitheliumWater reabsorptionRenal tubulesGlomerulotubular balanceInner earEndothelial cellsIon channelsHair cellsIntracellular signalingBone cellsCa(2TubulesPrimary ciliaIntracellular cytoskeletonCellsShear stressHydrodynamic forcesApical structuresFluid shear stressAltered renal proximal tubular endocytosis and histology in mice lacking myosin‐VI
Gotoh N, Yan Q, Du Z, Biemesderfer D, Kashgarian M, Mooseker MS, Wang T. Altered renal proximal tubular endocytosis and histology in mice lacking myosin‐VI. Cytoskeleton 2010, 67: 178-192. PMID: 20175219, PMCID: PMC3468331, DOI: 10.1002/cm.20435.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdaptor Proteins, Signal TransducingAdaptor Proteins, Vesicular TransportAnimalsApoptosis Regulatory ProteinsCell TransdifferentiationEndocytosisHorseradish PeroxidaseKidney Tubules, ProximalLow Density Lipoprotein Receptor-Related Protein-2MiceMice, Neurologic MutantsMicrofilament ProteinsMicrovilliMyosin Heavy ChainsVesicular Transport ProteinsConceptsProximal tubule cellsAlbumin excretionSv miceTubule cellsProximal tubule brush borderGlomerular flow rateProximal tubular dilationUrinary albumin excretionElevated blood pressureReduced body weightProximal tubular endocytosisRenal proximal tubule brush borderTubule brush borderProximal tubular uptakeBlood acid-base parametersMouse kidney proximal tubulesKidney proximal tubulesBlood pressureUrine volumeUrinary excretionAcid-base parametersRenal homogenatesTubular dilationPlasma concentrationsRenal clearance
2008
Neutrophil gelatinase-associated lipocalin suppresses cyst growth by Pkd1 null cells in vitro and in vivo
Wei F, Karihaloo A, Yu Z, Marlier A, Seth P, Shibazaki S, Wang T, Sukhatme VP, Somlo S, Cantley LG. Neutrophil gelatinase-associated lipocalin suppresses cyst growth by Pkd1 null cells in vitro and in vivo. Kidney International 2008, 74: 1310-1318. PMID: 18974761, PMCID: PMC3793389, DOI: 10.1038/ki.2008.395.Peer-Reviewed Original ResearchConceptsNeutrophil Gelatinase-Associated LipocalinCyst growthGelatinase-associated lipocalinAutosomal dominant polycystic kidney diseaseTubular cell proliferationDominant polycystic kidney diseaseCell linesPolycystic kidney diseasePkd1 mutant miceRenal functionAdenoviral delivery systemAssociated lipocalinKidney diseaseRate of proliferationCyst enlargementProliferative responseRenal epithelial cellsProximal tubulesMutant miceEpithelial cellsFlow stimuliCell proliferationDecreased rateApical ciliaProliferationShear-induced reorganization of renal proximal tubule cell actin cytoskeleton and apical junctional complexes
Duan Y, Gotoh N, Yan Q, Du Z, Weinstein A, Wang T, Weinbaum S. Shear-induced reorganization of renal proximal tubule cell actin cytoskeleton and apical junctional complexes. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 11418-11423. PMID: 18685100, PMCID: PMC2516248, DOI: 10.1073/pnas.0804954105.Peer-Reviewed Original ResearchConceptsProximal tubule cellsAdherens junctionsTight junctionsEndothelial cellsEpithelial cellsMouse proximal tubule cellsCell actin cytoskeletonDistribution of filamentous actinActin cytoskeletal reorganizationStress fiber disruptionActin-disrupting drugsApical junctional complexRenal epithelial cellsPeripheral actin bandsCuboidal epithelial cellsVascular endothelial cellsActin cytoskeletonFilamentous actinCytoskeletal reorganizationCytoskeletal responsesF-actinTubule cellsRenal epitheliumCytochalasin D.Water reabsorptionMouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins
Wagner CA, Loffing-Cueni D, Yan Q, Schulz N, Fakitsas P, Carrel M, Wang T, Verrey F, Geibel JP, Giebisch G, Hebert SC, Loffing J. Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins. American Journal Of Physiology. Renal Physiology 2008, 294: f1373-f1380. PMID: 18322017, DOI: 10.1152/ajprenal.00613.2007.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAnimalsBartter SyndromeCarrier ProteinsCation Transport ProteinsDinoprostoneDisease Models, AnimalEpithelial Sodium ChannelsKidney Tubules, DistalKidney Tubules, ProximalLoop of HenleMiceMice, Mutant StrainsPotassium Channels, Inwardly RectifyingReverse Transcriptase Polymerase Chain ReactionSodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSodium-Phosphate Cotransporter Proteins, Type IIaSodium-Potassium-Chloride SymportersSolute Carrier Family 12, Member 1Up-RegulationWaterConceptsThick ascending limbBartter's syndromeBartter-like phenotypeType II Bartter's syndromeWild-type miceAntenatal Bartter syndromeWild-type littermatesROMK null micePlasma aldosteroneMaternal polyhydramniosRenal sodiumVolume depletionRenal tubulopathyMouse modelSemiquantitative immunoblottingProximal tubulesAscending limbKidney homogenatesSyndromeHenle's loopNull miceDCT cellsWater transport proteinsCompensatory mechanismsMice
2007
NHE3 phosphorylation at serines 552 and 605 does not directly affect NHE3 activity
Kocinsky HS, Dynia DW, Wang T, Aronson PS. NHE3 phosphorylation at serines 552 and 605 does not directly affect NHE3 activity. American Journal Of Physiology. Renal Physiology 2007, 293: f212-f218. PMID: 17409282, DOI: 10.1152/ajprenal.00042.2007.Peer-Reviewed Original ResearchMeSH Keywords1-Methyl-3-isobutylxanthineAnimalsCells, CulturedColforsinCyclic AMP-Dependent Protein KinasesElectrophoresis, Polyacrylamide GelKidneyKidney Tubules, ProximalMaleMicrovilliParathyroid HormonePhosphodiesterase InhibitorsPhosphorylationRatsRats, Sprague-DawleySerineSodiumSodium RadioisotopesSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersStimulation, ChemicalConceptsSerine 552NHE3 phosphorylationNHE3 activityMicrovillar membrane vesiclesPhosphorylation of NHE3Direct phosphorylationPhosphospecific antibodiesSprague-Dawley ratsExchanger type 3PKA activationMembrane vesiclesSite-specific changesPhosphorylationTransport activityOpossum kidney cellsParathyroid hormoneIntravenous infusionRat modelExchange activityKidney cellsOKP cellsNHE3 inhibitionPKACell modelExact roleFlow-dependent transport in a mathematical model of rat proximal tubule
Weinstein A, Weinbaum S, Duan Y, Du Z, Yan Q, Wang T. Flow-dependent transport in a mathematical model of rat proximal tubule. American Journal Of Physiology. Renal Physiology 2007, 292: f1164-f1181. PMID: 17213461, DOI: 10.1152/ajprenal.00392.2006.Peer-Reviewed Original ResearchConceptsNa(+) reabsorptionRat proximal tubulesProximal tubulesModel tubuleDiuretic effectMouse proximal tubuleLuminal perfusion rateLow flowsSolute transportNaCl reabsorptionPeritubular transportTranscellular NaCl reabsorptionCarbonic anhydrase inhibitionGlomerulotubular balanceTubulesReabsorptionTransporter densityLuminal flowModel calculationsRatsFlow-dependent transportTransporter insertionMathematical modelPerfusion rateRate of hydration
2006
Flow-activated transport events along the nephron
Wang T. Flow-activated transport events along the nephron. Current Opinion In Nephrology & Hypertension 2006, 15: 530-536. PMID: 16914967, DOI: 10.1097/01.mnh.0000242180.46362.c4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBicarbonatesBiological TransportHumansKidney Tubules, ProximalMicrovilliNephronsSodiumConceptsBrush-border microvilliProximal tubulesCultured proximal tubule cellsProximal tubules in vitroGlomerular filtration rateProximal tubule cellsBrush-borderH-ATPase activityTubules in vitroNHE3 activityHCO3- absorptionENOS translocationTubule cellsFiltration rateMg2+ transportReceptor localizationSignal transduction mechanismsH-ATPaseHormonal regulationCa2+NephronTubulesResponse to flowTransduction mechanismsIntact actin cytoskeleton
2005
Axial flow modulates proximal tubule NHE3 and H-ATPase activities by changing microvillus bending moments
Du Z, Yan Q, Duan Y, Weinbaum S, Weinstein A, Wang T. Axial flow modulates proximal tubule NHE3 and H-ATPase activities by changing microvillus bending moments. American Journal Of Physiology. Renal Physiology 2005, 290: f289-f296. PMID: 16144961, DOI: 10.1152/ajprenal.00255.2005.Peer-Reviewed Original ResearchConceptsProximal tubules in vitroHCO3- absorptionTubules in vitroBrush-border microvilliHCO3- permeabilityH(+)-ATPase inhibitor bafilomycinInhibition of NHE3Proximal tubule NHE3Transepithelial potential differenceH-ATPase activityLuminal cell membraneH(+)-ATPaseTransepithelial PDNa+ absorptionParacellular permeabilityH(+)-ATPase activityInhibitor EIPAMembrane transport activityProximal tubulesHCO3- reabsorptionNHE3HCO3- transportH-ATPaseBicarbonate transportPermeability changes