2024
Interleukin-16 is increased in dialysis patients but is not a cardiovascular risk factor
Brösecke F, Pfau A, Ermer T, Dein Terra Mota Ribeiro A, Rubenbauer L, Rao V, Burlein S, Genser B, Reichel M, Aronson P, Coca S, Knauf F. Interleukin-16 is increased in dialysis patients but is not a cardiovascular risk factor. Scientific Reports 2024, 14: 11323. PMID: 38760468, PMCID: PMC11101424, DOI: 10.1038/s41598-024-61808-7.Peer-Reviewed Original ResearchConceptsIL-16 levelsIL-16Dialysis patientsCardiovascular eventsConcentrations of IL-16Kidney failureUremic toxinsCardiovascular diseaseCompared to healthy individualsPlasma oxalate concentrationActivated immune cellsAssociated with cardiovascular diseaseIL-16 concentrationCytokine IL-16Cardiovascular risk factorsNo significant associationPlasma oxalateInflammatory markersImmune cellsCytokine concentrationsInterleukin-16US patientsCohort 1Cardiovascular outcomesHealthy individuals
2021
High Oxalate Concentrations Correlate with Increased Risk for Sudden Cardiac Death in Dialysis Patients
Pfau A, Ermer T, Coca S, Tio MC, Genser B, Reichel M, Finkelstein FO, März W, Wanner C, Waikar SS, Eckardt KU, Aronson P, Drechsler C, Knauf F. High Oxalate Concentrations Correlate with Increased Risk for Sudden Cardiac Death in Dialysis Patients. Journal Of The American Society Of Nephrology 2021, 32: 2375-2385. PMID: 34281958, PMCID: PMC8729829, DOI: 10.1681/asn.2020121793.Peer-Reviewed Original ResearchConceptsSudden cardiac deathCardiac deathCardiovascular eventsKidney failurePrimary composite cardiovascular end pointComposite cardiovascular end pointGerman Diabetes Dialysis StudyCox proportional hazards modelCardiovascular end pointsCohort of patientsNovel risk factorsProportional hazards modelCubic spline modelingCause mortalityChronic dialysisCardiovascular mortalityDialysis patientsStudy cohortUS patientsRisk regressionRisk factorsEuropean patientsSerum oxalate concentrationClinical significanceSeparate cohortDeletion 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
2020
Enteric Oxalate Secretion Mediated by Slc26a6 Defends against Hyperoxalemia in Murine Models of Chronic Kidney Disease
Neumeier LI, Thomson RB, Reichel M, Eckardt KU, Aronson PS, Knauf F. Enteric Oxalate Secretion Mediated by Slc26a6 Defends against Hyperoxalemia in Murine Models of Chronic Kidney Disease. Journal Of The American Society Of Nephrology 2020, 31: 1987-1995. PMID: 32660969, PMCID: PMC7461683, DOI: 10.1681/asn.2020010105.Peer-Reviewed Original ResearchConceptsEnteric oxalate secretionPlasma oxalate concentrationOxalate secretionModel of CKDChronic kidney diseaseIntestine of miceWild-type miceHealthy kidney functionOxalate clearanceWestern blot analysisKidney injuryKidney functionOxalate excretionWeekly injectionsKidney diseaseCKD modelExtrarenal clearanceOxalate transporter SLC26A6CKDMurine modelSignificant elevationOxalate homeostasisTransporter expressionMiceProtein expression
2018
Characterization of renal NaCl and oxalate transport in Slc26a6−/− mice
Knauf F, Velazquez H, Pfann V, Jiang Z, Aronson PS. Characterization of renal NaCl and oxalate transport in Slc26a6−/− mice. American Journal Of Physiology. Renal Physiology 2018, 316: f128-f133. PMID: 30427220, PMCID: PMC6383200, DOI: 10.1152/ajprenal.00309.2018.Peer-Reviewed Original ResearchConceptsWild-type miceNaCl homeostasisBlood pressureProximal tubulesFree-flow micropuncture studiesSurface proximal tubulesLow-salt dietMean blood pressureLower blood pressureUrine flow rateLack of effectFurosemide infusionNet renal secretionSodium excretionUrine oxalateFractional excretionMicropuncture studiesNaCl deliveryRenal secretionApical membrane ClExchanger SLC26A6MiceRenal NaClNaCl transportHomeostasis
2016
N-glycosylation critically regulates function of oxalate transporter SLC26A6
Thomson RB, Thomson CL, Aronson PS. N-glycosylation critically regulates function of oxalate transporter SLC26A6. American Journal Of Physiology - Cell Physiology 2016, 311: c866-c873. PMID: 27681177, PMCID: PMC5206297, DOI: 10.1152/ajpcell.00171.2016.Peer-Reviewed Original ResearchConceptsPlasma membraneIntegral membrane proteinsCell surface deliverySLC26A6 functionTissue-specific differencesGlycosylation mutantsMembrane proteinsN-glycosylationSurface deliveryBiotinylation studiesOxalate transporterOxalate homeostasisSecond extracellular loopExtracellular loopIntact cellsEnzymatic deglycosylation studiesTransport activityEnzymatic deglycosylationFunctional studiesDeglycosylation studiesGlycosylationPutative second extracellular loopTransport functionFunctional significanceEssential role
2013
NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy
Knauf F, Asplin JR, Granja I, Schmidt IM, Moeckel GW, David RJ, Flavell RA, Aronson PS. NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy. Kidney International 2013, 84: 895-901. PMID: 23739234, PMCID: PMC3772982, DOI: 10.1038/ki.2013.207.Peer-Reviewed Original ResearchConceptsProgressive renal failureRenal failureCalcium oxalate crystal depositionCrystal-associated diseasesOverproduction of oxalateWild-type miceHigh-oxalate dietNephropathy resultsOxalate nephropathyRenal histologyKidney diseaseOxalate dietInflammatory responseNALP3 expressionDietary oxalateIntestinal oxalateOxalate homeostasisSoluble oxalateNephropathyCrystal depositionMiceMultiple disordersNALP3DietInflammationEzrin Is Required for the Functional Regulation of the Epithelial Sodium Proton Exchanger, NHE3
Hayashi H, Tamura A, Krishnan D, Tsukita S, Suzuki Y, Kocinsky HS, Aronson PS, Orlowski J, Grinstein S, Alexander RT. Ezrin Is Required for the Functional Regulation of the Epithelial Sodium Proton Exchanger, NHE3. PLOS ONE 2013, 8: e55623. PMID: 23405179, PMCID: PMC3566197, DOI: 10.1371/journal.pone.0055623.Peer-Reviewed Original ResearchMeSH KeywordsActin CytoskeletonAnimalsColonCyclic AMPCytoskeletal ProteinsDogsEpithelial CellsFluorescence Recovery After PhotobleachingHumansMadin Darby Canine Kidney CellsMaleMembrane ProteinsMiceMice, KnockoutMicrofilament ProteinsMicrovilliOctoxynolPhosphorylationProtein TransportRNA, Small InterferingSodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersConceptsApical actin cytoskeletonNHE3 activitySodium hydrogen exchanger isoform 3CAMP-dependent inhibitionEzrin knockdown miceERM proteinsActin cytoskeletonSodium-proton exchangerApical cytoskeletonApical localizationFunctional regulationWild-type animalsEpithelial cell culture modelEzrinProton exchangersFluorescent recoveryEpithelial phenotypeCytoskeletonMolecular determinantsCell culture modelExchanger isoform 3Functional studiesNon-targeting siRNAApical membraneIsoform 3
2012
Urinary Metabolic Phenotyping the slc26a6 (Chloride–Oxalate Exchanger) Null Mouse Model
Garcia-Perez I, Villaseñor A, Wijeyesekera A, Posma JM, Jiang Z, Stamler J, Aronson P, Unwin R, Barbas C, Elliott P, Nicholson J, Holmes E. Urinary Metabolic Phenotyping the slc26a6 (Chloride–Oxalate Exchanger) Null Mouse Model. Journal Of Proteome Research 2012, 11: 4425-4435. PMID: 22594923, PMCID: PMC4028149, DOI: 10.1021/pr2012544.Peer-Reviewed Original ResearchConceptsRenal stone diseaseStone diseaseNull miceUrinary metabolic signaturesBlood pressure controlWild-type miceNull mouse modelRenal stone formationRenal proximal tubulesUrinary metabolicUrinary metabolomeClear metabolic differentiationSodium homeostasisRenal stonesType miceMouse modelUrinary metabolitesOxalate balanceUrinary profilesProximal tubulesPressure controlStone formationExchanger SLC26A6Metabolic signaturesPathological processes
2008
Phenotypic and Functional Analysis of Human SLC26A6 Variants in Patients With Familial Hyperoxaluria and Calcium Oxalate Nephrolithiasis
Monico CG, Weinstein A, Jiang Z, Rohlinger AL, Cogal AG, Bjornson BB, Olson JB, Bergstralh EJ, Milliner DS, Aronson PS. Phenotypic and Functional Analysis of Human SLC26A6 Variants in Patients With Familial Hyperoxaluria and Calcium Oxalate Nephrolithiasis. American Journal Of Kidney Diseases 2008, 52: 1096-1103. PMID: 18951670, PMCID: PMC2710965, DOI: 10.1053/j.ajkd.2008.07.041.Peer-Reviewed Original ResearchConceptsPrimary hyperoxaluria type 1Oxalate transportMajor risk factorCalcium oxalate nephrolithiasisUrine oxalate levelsCalcium oxalate urolithiasisRare variantsHyperoxaluria type 1Calcium oxalate stonesAdditional missense variantsUrine oxalateOxalate excretionRisk factorsOxalate nephrolithiasisOxalate urolithiasisHyperoxaluriaAbstractTextAdult subjectsType 1Oxalate stonesPotential modifiersStudy designOxalate levelsGood healthMissense variants
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 role
2006
Pendrin Regulation in Mouse Kidney Primarily Is Chloride-Dependent
Vallet M, Picard N, Loffing-Cueni D, Fysekidis M, Bloch-Faure M, Deschênes G, Breton S, Meneton P, Loffing J, Aronson PS, Chambrey R, Eladari D. Pendrin Regulation in Mouse Kidney Primarily Is Chloride-Dependent. Journal Of The American Society Of Nephrology 2006, 17: 2153-2163. PMID: 16825334, DOI: 10.1681/asn.2005101054.Peer-Reviewed Original ResearchConceptsHydrochlorothiazide administrationAldosterone secretionExtracellular fluid volume regulationElevated plasma aldosterone levelsPlasma aldosterone levelsDifferent mouse modelsFluid volume regulationPendrin protein expressionAldosterone levelsSecondary hyperaldosteronismEpithelial sodium channelChloride transportApical Cl-/HCO3Chloride reabsorptionRat modelPendrin expressionMouse modelKnockout miceSemiquantitative immunoblottingNaCl loadingGamma-ENaC subunitsBiologic effectsExperimental modelSodium channelsProtein expression
2005
Use of phospho-specific antibodies to determine the phosphorylation of endogenous Na+/H+ exchanger NHE3 at PKA consensus sites
Kocinsky HS, Girardi AC, Biemesderfer D, Nguyen T, Mentone S, Orlowski J, Aronson PS. Use of phospho-specific antibodies to determine the phosphorylation of endogenous Na+/H+ exchanger NHE3 at PKA consensus sites. American Journal Of Physiology. Renal Physiology 2005, 289: f249-f258. PMID: 15687252, DOI: 10.1152/ajprenal.00082.2004.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesAntibodies, MonoclonalAntibody SpecificityCell LineChlorocebus aethiopsCOS CellsCyclic AMP-Dependent Protein KinasesDopamineElectrophoresis, Polyacrylamide GelImmunohistochemistryKidneyMaleMiceMice, Inbred BALB CMicroscopy, FluorescenceMicrovilliOpossumsPhosphorylationRatsRats, Sprague-DawleySodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSubcellular FractionsTransfectionConceptsSerine 552Total NHE3Brush border membranePKA consensus sitesEffects of dopamineProximal tubule cellsWestern blot assaysOpossum kidney cellsBaseline phosphorylationPeptide antibodiesInhibition of NHE3Tubule cellsBlot assaysAntibodiesPhosphorylation of NHE3Phosphospecific antibodiesExchanger NHE3NHE3DopamineEndogenous NHE3Kidney cellsVivoPhospho-specific antibodiesTransfection studiesVitro
2004
The Cl−/HCO3− exchanger pendrin in the rat kidney is regulated in response to chronic alterations in chloride balance
Quentin F, Chambrey R, Trinh-Trang-Tan MM, Fysekidis M, Cambillau M, Paillard M, Aronson PS, Eladari D. The Cl−/HCO3− exchanger pendrin in the rat kidney is regulated in response to chronic alterations in chloride balance. American Journal Of Physiology. Renal Physiology 2004, 287: f1179-f1188. PMID: 15292050, DOI: 10.1152/ajprenal.00211.2004.Peer-Reviewed Original ResearchConceptsChronic furosemide administrationBlood pressure regulationDiet-induced changesAcid-base statusNaCl dietFurosemide administrationChronic alterationsControl ratsRenal membrane fractionsChloride balanceChronic changesNaCl balanceExchanger pendrinSemiquantitative immunoblottingPressure regulationRat kidneyConsistent inverse relationshipPD expressionNaCl depletionType BProtein abundanceRatsPendrinInverse relationshipExpression
2002
Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status
Wagner CA, Finberg KE, Stehberger PA, Lifton RP, Giebisch GH, Aronson PS, Geibel JP. Regulation of the expression of the Cl-/anion exchanger pendrin in mouse kidney by acid-base status. Kidney International 2002, 62: 2109-2117. PMID: 12427135, DOI: 10.1046/j.1523-1755.2002.00671.x.Peer-Reviewed Original ResearchConceptsPendrin-positive cellsAcid-base statusPositive cellsBicarbonate secretionMouse kidneyAcid-base transportKnockout mouse modelProtein expression levelsMetabolic alkalosisDeficient dietExchanger pendrinPendrin expressionMouse modelSensorineural deafnessThyroid glandBicarbonate loadPendred syndromeWestern blottingApical membraneInner earPendrin proteinControl levelsKidneyPendrinProtein levelsFormate-stimulated NaCl absorption in the proximal tubule is independent of the pendrin protein
Karniski LP, Wang T, Everett LA, Green ED, Giebisch G, Aronson PS. Formate-stimulated NaCl absorption in the proximal tubule is independent of the pendrin protein. American Journal Of Physiology. Renal Physiology 2002, 283: f952-f956. PMID: 12372770, DOI: 10.1152/ajprenal.00182.2002.Peer-Reviewed Original ResearchConceptsProximal tubulesChloride/formate exchangeNaCl reabsorptionChloride reabsorptionElectroneutral NaCl reabsorptionNaCl absorptionRole of pendrinFormate exchangePds-knockout mouseRecycling of formatePendrin proteinReabsorptionMicePendrinBrush border membrane vesiclesTubulesPresent studyChloride transportApical membrane
2001
Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron
Wang T, Hropot M, Aronson P, Giebisch G. Role of NHE isoforms in mediating bicarbonate reabsorption along the nephron. American Journal Of Physiology. Renal Physiology 2001, 281: f1117-f1122. PMID: 11704563, DOI: 10.1152/ajprenal.2001.281.6.f1117.Peer-Reviewed Original ResearchConceptsLoop of HenleHOE 694Proximal tubulesAddition of ethylisopropylamilorideDistal convoluted tubuleBicarbonate reabsorptionConvoluted tubulesSitu microperfusionRat kidneySignificant inhibitionNHE isoformsHenlePredominant isoformTubulesNHE3Functional roleInhibitionNHE2Apical membraneIsoformsApical isoformKidneyMicroperfusionEthylisopropylamilorideNephronRole of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes
Mennone A, Biemesderfer D, Negoianu D, Yang C, Abbiati T, Schultheis P, Shull G, Aronson P, Boyer J. Role of sodium/hydrogen exchanger isoform NHE3 in fluid secretion and absorption in mouse and rat cholangiocytes. AJP Gastrointestinal And Liver Physiology 2001, 280: g247-g254. PMID: 11208547, DOI: 10.1152/ajpgi.2001.280.2.g247.Peer-Reviewed Original Research
2000
Active (9.6 S) and Inactive (21 S) Oligomers of NHE3 in Microdomains of the Renal Brush Border*
Biemesderfer D, DeGray B, Aronson P. Active (9.6 S) and Inactive (21 S) Oligomers of NHE3 in Microdomains of the Renal Brush Border*. Journal Of Biological Chemistry 2000, 276: 10161-10167. PMID: 11120742, DOI: 10.1074/jbc.m008098200.Peer-Reviewed Original ResearchAcridine OrangeAnimalsAntibodiesCarrier ProteinsCell MembraneCentrifugation, Density GradientElectrophoresis, Polyacrylamide GelEndosomesFluorescent Antibody Technique, IndirectGoatsHeymann Nephritis Antigenic ComplexHydrogenHydrogen-Ion ConcentrationImmunoblottingImmunohistochemistryKidneyKidney TubulesMagnesiumMaleMembrane GlycoproteinsMicrofilament ProteinsMicroscopy, ElectronMicrovilliMitochondriaPrecipitin TestsProtein BindingProtein Structure, TertiaryRabbitsRatsRats, Sprague-DawleySodiumSodium-Hydrogen Exchanger 3Sodium-Hydrogen ExchangersSucroseTime Factors
1999
Specific Association of Megalin and the Na+/H+ Exchanger Isoform NHE3 in the Proximal Tubule*
Biemesderfer D, Nagy T, DeGray B, Aronson P. Specific Association of Megalin and the Na+/H+ Exchanger Isoform NHE3 in the Proximal Tubule*. Journal Of Biological Chemistry 1999, 274: 17518-17524. PMID: 10364184, DOI: 10.1074/jbc.274.25.17518.Peer-Reviewed Original Research