2023
APOBEC-1 deletion enhances cisplatin-induced acute kidney injury
Guo X, Blanc V, Davidson N, Velazquez H, Chen T, Moledina D, Moeckel G, Safirstein R, Desir G. APOBEC-1 deletion enhances cisplatin-induced acute kidney injury. Scientific Reports 2023, 13: 22255. PMID: 38097707, PMCID: PMC10721635, DOI: 10.1038/s41598-023-49575-3.Peer-Reviewed Original Research
2017
Loss of the podocyte glucocorticoid receptor exacerbates proteinuria after injury
Zhou H, Tian X, Tufro A, Moeckel G, Ishibe S, Goodwin J. Loss of the podocyte glucocorticoid receptor exacerbates proteinuria after injury. Scientific Reports 2017, 7: 9833. PMID: 28852159, PMCID: PMC5575043, DOI: 10.1038/s41598-017-10490-z.Peer-Reviewed Original ResearchConceptsKnockout miceGlucocorticoid receptorNephrotic syndromeSimilar renal functionMainstay of therapyReceptor knockout miceTreatment of proteinuriaFoot process effacementMechanism of actionImmunomodulatory therapyRenal functionGlomerular injuryProtein excretionKO miceCommon disorderNephrotoxic serumPodocyte injuryPodocyte-specific deletionMouse modelSlit diaphragm proteinsWild-type podocytesProcess effacementProteinuriaUnstimulated conditionsKnockout animalsMIF-2/D-DT enhances proximal tubular cell regeneration through SLPI- and ATF4-dependent mechanisms
Ochi A, Chen D, Schulte W, Leng L, Moeckel N, Piecychna M, Averdunk L, Stoppe C, Bucala R, Moeckel G. MIF-2/D-DT enhances proximal tubular cell regeneration through SLPI- and ATF4-dependent mechanisms. American Journal Of Physiology. Renal Physiology 2017, 313: f767-f780. PMID: 28539339, PMCID: PMC6148305, DOI: 10.1152/ajprenal.00683.2016.Peer-Reviewed Original ResearchMeSH KeywordsActivating Transcription Factor 4Acute Kidney InjuryAnimalsAntigens, Differentiation, B-LymphocyteApoptosisAutophagyCell HypoxiaCell LineCell ProliferationCyclin D1Disease Models, AnimalEukaryotic Initiation Factor-2FemaleGenetic Predisposition to DiseaseHistocompatibility Antigens Class IIIntramolecular OxidoreductasesKidney Tubules, ProximalMacrophage Migration-Inhibitory FactorsMaleMice, Inbred C57BLMice, KnockoutPhenotypeRegenerationReperfusion InjurySecretory Leukocyte Peptidase InhibitorSignal TransductionTime FactorsTransfectionConceptsMacrophage migration inhibitory factorSecretory leukocyte proteinase inhibitorTubular cell regenerationProximal tubular cellsD-DTCell regenerationTubular cellsIschemic acute kidney injuryIschemia-reperfusion injury modelWild-type control miceMouse proximal tubular cellsAcute kidney injuryIschemia-reperfusion injuryRenal proximal tubular cellsMigration inhibitory factorIntegrated stress responseATF4-dependent mechanismCyclin D1 expressionEukaryotic initiation factorKidney injuryTubular injuryControl miceChemokine receptorsInjury modelInflammatory context
2015
Human Polycystin-2 Transgene Dose-Dependently Rescues ADPKD Phenotypes in Pkd2 Mutant Mice
Li A, Tian X, Zhang X, Huang S, Ma Y, Wu D, Moeckel G, Somlo S, Wu G. Human Polycystin-2 Transgene Dose-Dependently Rescues ADPKD Phenotypes in Pkd2 Mutant Mice. American Journal Of Pathology 2015, 185: 2843-2860. PMID: 26435415, PMCID: PMC4607765, DOI: 10.1016/j.ajpath.2015.06.014.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseaseMouse modelADPKD phenotypeSevere cystic phenotypeWild-type miceDose-dependent mannerPolycystic kidney diseaseForms of ADPKDKidney diseasePancreatic cystsEffective treatmentFunctional restorationMutant miceTransgene doseMiceCyst formationReduced proliferationEpithelial cellsCystic phenotypeKidneyLiverFurther ameliorationPC2 activityPhenotypeMolecular genetic mechanisms
2014
Semaphorin3a Promotes Advanced Diabetic Nephropathy
Aggarwal PK, Veron D, Thomas DB, Siegel D, Moeckel G, Kashgarian M, Tufro A. Semaphorin3a Promotes Advanced Diabetic Nephropathy. Diabetes 2014, 64: 1743-1759. PMID: 25475434, PMCID: PMC4407856, DOI: 10.2337/db14-0719.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsChromonesCollagen Type IVDiabetes Mellitus, ExperimentalDiabetic NephropathiesEnzyme-Linked Immunosorbent AssayGene Expression RegulationGene Knockdown TechniquesHumansIntegrin alphaVbeta3LamininMembrane ProteinsMiceMice, KnockoutMicrofilament ProteinsMicrotubule-Associated ProteinsMixed Function OxygenasesNerve Tissue ProteinsPodocytesProteinuriaReceptors, Cell SurfaceRenal InsufficiencySemaphorin-3AWT1 ProteinsXanthonesConceptsAdvanced diabetic nephropathyDiabetic nephropathyRenal insufficiencyDiffuse podocyte foot process effacementPodocyte foot process effacementSevere diabetic nephropathyCollagen IV accumulationPotential therapeutic targetFoot process effacementGlomerular nodulesKimmelstiel-WilsonRenal biopsyGlomerular filtration barrierNodular glomerulosclerosisDiabetic miceMassive proteinuriaNovel therapiesDisease outcomePathogenic factorsTargetable pathwaysTherapeutic targetProcess effacementBarrier abnormalitiesFunction miceNephropathyLoss of Polycystin-1 Inhibits Bicc1 Expression during Mouse Development
Lian P, Li A, Li Y, Liu H, Liang D, Hu B, Lin D, Jiang T, Moeckel G, Qin D, Wu G. Loss of Polycystin-1 Inhibits Bicc1 Expression during Mouse Development. PLOS ONE 2014, 9: e88816. PMID: 24594709, PMCID: PMC3940423, DOI: 10.1371/journal.pone.0088816.Peer-Reviewed Original ResearchConceptsAutosomal dominant polycystic kidney diseasePolycystic kidney diseasePolycystin-1Gene productsKidney developmentKidney diseaseRNA-binding proteinMouse kidney developmentPKD1 gene productEmbryonic day 8.5Human autosomal dominant polycystic kidney diseaseNew molecular linkTemporal expression patternsEarly ureteric budDominant polycystic kidney diseaseC. elegansHuman polycystic kidney diseaseMouse embryogenesisMouse developmentPostnatal kidney developmentMouse homologueCystic phenotypeExpression patternsMolecular linkMultiple speciesPodocyte-Specific VEGF-A Gain of Function Induces Nodular Glomerulosclerosis in eNOS Null Mice
Veron D, Aggarwal PK, Velazquez H, Kashgarian M, Moeckel G, Tufro A. Podocyte-Specific VEGF-A Gain of Function Induces Nodular Glomerulosclerosis in eNOS Null Mice. Journal Of The American Society Of Nephrology 2014, 25: 1814-1824. PMID: 24578128, PMCID: PMC4116059, DOI: 10.1681/asn.2013070752.Peer-Reviewed Original ResearchConceptsNodular glomerulosclerosisGain of functionEndothelial nitric oxide synthase knockout miceNitric oxide synthase knockout miceGlomerular basement membrane thickeningENOS-null miceSynthase knockout miceBasement membrane thickeningWild-type miceCollagen IVArteriolar hyalinosisGlomerular nodulesGlomerular VEGFKimmelstiel-WilsonPronounced albuminuriaCreatinine clearanceRenal failureDiabetic nephropathyENOS deficiencyMassive proteinuriaDiabetic milieuMembrane thickeningPodocyte effacementDeposition of lamininKnockout micePodocyte-associated talin1 is critical for glomerular filtration barrier maintenance
Tian X, Kim JJ, Monkley SM, Gotoh N, Nandez R, Soda K, Inoue K, Balkin DM, Hassan H, Son SH, Lee Y, Moeckel G, Calderwood DA, Holzman LB, Critchley DR, Zent R, Reiser J, Ishibe S. Podocyte-associated talin1 is critical for glomerular filtration barrier maintenance. Journal Of Clinical Investigation 2014, 124: 1098-1113. PMID: 24531545, PMCID: PMC3934159, DOI: 10.1172/jci69778.Peer-Reviewed Original ResearchConceptsNephrotic syndromeFoot process effacementLoss of talin1Glomerular filtration barrierGlomerular injuryMurine modelProcess effacementKidney's glomerular filtration barrierFiltration barrierGlomerular basement membraneSevere proteinuriaKidney failurePharmacologic inhibitionSyndromeBarrier maintenanceCalpain activityIntegrin activationEpithelial cellsPodocytesModest reductionΒ1 integrin activationBasement membranePathogenesisInjuryCytoskeletal protein talin1Renalase Prevents AKI Independent of Amine Oxidase Activity
Wang L, Velazquez H, Moeckel G, Chang J, Ham A, Lee HT, Safirstein R, Desir GV. Renalase Prevents AKI Independent of Amine Oxidase Activity. Journal Of The American Society Of Nephrology 2014, 25: 1226-1235. PMID: 24511138, PMCID: PMC4033373, DOI: 10.1681/asn.2013060665.Peer-Reviewed Original ResearchConceptsIschemic injuryCatecholamine levelsRecombinant renalaseAmine oxidase activityHuman proximal tubular cellsCisplatin-induced AKITreatment of AKIWild-type miceHK-2 cellsProximal tubular cellsOxidase activityKidney injuryRenal injuryC-Jun N-terminal kinaseExtracellular signal-regulated kinaseP38 mitogen-activated protein kinaseToxic injuryRenalase proteinTubular cellsSignal-regulated kinaseIntracellular signaling cascadesRenalaseInjuryMitogen-activated protein kinaseN-terminal kinase
2013
Early B-cell factor 1 is an essential transcription factor for postnatal glomerular maturation
Fretz JA, Nelson T, Velazquez H, Xi Y, Moeckel GW, Horowitz MC. Early B-cell factor 1 is an essential transcription factor for postnatal glomerular maturation. Kidney International 2013, 85: 1091-1102. PMID: 24172684, PMCID: PMC4006322, DOI: 10.1038/ki.2013.433.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAlbuminuriaAnimalsBlood Urea NitrogenCell DifferentiationCells, CulturedGene Expression Regulation, DevelopmentalGenotypeGlomerular Filtration RateKidney GlomerulusMice, 129 StrainMice, Inbred C57BLMice, KnockoutOrganogenesisPhenotypePodocytesSignal TransductionTime FactorsTrans-ActivatorsVascular Endothelial Growth Factor AConceptsEarly B-cell factor 1B cell factor 1Transcription factorsNovel roleTranscription factor early B cell factor 1Expression of Ebf1Essential transcription factorFactor 1Podocyte maturationMesenchymal progenitorsB cell maturationProper maturationBlood urea nitrogen levelsElevated blood urea nitrogen levelsWild-type control miceGlomerular filtration rateVascular endothelial growth factor AGlomerular maturationUrea nitrogen levelsGrowth factor ARenal developmentEBF1Factor AGlomerular developmentNephron maturationMet Activation Is Required for Early Cytoprotection after Ischemic Kidney Injury
Mason S, Hader C, Marlier A, Moeckel G, Cantley LG. Met Activation Is Required for Early Cytoprotection after Ischemic Kidney Injury. Journal Of The American Society Of Nephrology 2013, 25: 329-337. PMID: 24136921, PMCID: PMC3904569, DOI: 10.1681/asn.2013050473.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAnimalsApoptosisBcl-Associated Death ProteinGene Knockdown TechniquesKidneyKidney Tubules, ProximalMAP Kinase Signaling SystemMiceMice, Inbred C57BLMice, KnockoutOrgan SpecificityPhosphatidylinositol 3-KinasesPhosphorylationProtein Processing, Post-TranslationalProto-Oncogene Proteins c-aktReceptor Protein-Tyrosine KinasesReperfusion InjuryRibosomal Protein S6 Kinases, 70-kDaSignal TransductionConceptsIschemia/reperfusionKidney injuryIschemic injuryProximal tubulesInitial tubular injuryMET receptor expressionProximal tubule responseTubular cell survivalIschemic kidney injuryProximal tubule epithelial cellsRenal proximal tubule epithelial cellsTubular cell proliferationTubular cell apoptosisPI3K/Akt activationProapoptotic factor BadTubule epithelial cellsCell survivalTubule responseSerum creatinineTubular injuryKidney repairLiver abnormalitiesReceptor expressionInjuryMET activationNALP3-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 disordersNALP3DietInflammation
2012
Role of dynamin, synaptojanin, and endophilin in podocyte foot processes
Soda K, Balkin DM, Ferguson SM, Paradise S, Milosevic I, Giovedi S, Volpicelli-Daley L, Tian X, Wu Y, Ma H, Son SH, Zheng R, Moeckel G, Cremona O, Holzman LB, De Camilli P, Ishibe S. Role of dynamin, synaptojanin, and endophilin in podocyte foot processes. Journal Of Clinical Investigation 2012, 122: 4401-4411. PMID: 23187129, PMCID: PMC3533561, DOI: 10.1172/jci65289.Peer-Reviewed Original ResearchConceptsRole of dynaminNormal embryonic developmentFiltration barrierSynaptic vesicle recyclingFoot process formationKidney filtration barrierGlomerular filtration barrierNeuronal synapse developmentDynamin's roleEndophilin 3Actin cytoskeletonActin dynamicsFunctional partnersDynamin 1Endophilin-1Embryonic developmentVesicle recyclingProtein networkKidney's glomerular filtration barrierSynapse developmentDynaminPodocyte foot processesNeuronal synapsesSynaptojaninEndophilinIntrarenal Dopamine Inhibits Progression of Diabetic Nephropathy
Zhang MZ, Yao B, Yang S, Yang H, Wang S, Fan X, Yin H, Fogo AB, Moeckel GW, Harris RC. Intrarenal Dopamine Inhibits Progression of Diabetic Nephropathy. Diabetes 2012, 61: 2575-2584. PMID: 22688335, PMCID: PMC3447896, DOI: 10.2337/db12-0046.Peer-Reviewed Original ResearchConceptsIntrarenal dopaminergic systemRenal dopamine productionDopaminergic systemDopamine productionDiabetic nephropathyDiabetic miceWild-type diabetic miceOxidative stressDiabetic kidney injuryIntrarenal dopamine productionRenin-angiotensin systemMarkers of inflammationType 1 diabetesAromatic amino acid decarboxylaseCyclooxygenase-2 expressionKidney injuryRenal hemodynamicsRenal transplantationUnderlying pathogenesisDopamine metabolismInhibition of expressionInhibits progressionAmino acid decarboxylaseFluid reabsorptionKidney structure
2011
SGLT2 Deletion Improves Glucose Homeostasis and Preserves Pancreatic β-Cell Function
Jurczak MJ, Lee HY, Birkenfeld AL, Jornayvaz FR, Frederick DW, Pongratz RL, Zhao X, Moeckel GW, Samuel VT, Whaley JM, Shulman GI, Kibbey RG. SGLT2 Deletion Improves Glucose Homeostasis and Preserves Pancreatic β-Cell Function. Diabetes 2011, 60: 890-898. PMID: 21357472, PMCID: PMC3046850, DOI: 10.2337/db10-1328.Peer-Reviewed Original ResearchConceptsHigh-fat dietPancreatic β-cell functionΒ-cell functionDb/db backgroundKnockout miceGlucose intoleranceGlucose homeostasisPreserves pancreatic β-cell functionDb/db miceImproved glucose intoleranceGlucose-stimulated insulin secretionRenal glucose excretionPrevention of hyperglycemiaRenal glucose reabsorptionType 2 diabetesDb backgroundPlasma insulin concentrationCotransporter type 2Β-cell massObesity-associated hyperglycemiaΒ-cell deathRegular chowGlucose excretionUrine outputSGLT2 inhibition
2010
Identification and Regulation of Reticulon 4B (Nogo-B) in Renal Tubular Epithelial Cells
Marin EP, Moeckel G, Al-Lamki R, Bradley J, Yan Q, Wang T, Wright PL, Yu J, Sessa WC. Identification and Regulation of Reticulon 4B (Nogo-B) in Renal Tubular Epithelial Cells. American Journal Of Pathology 2010, 177: 2765-2773. PMID: 20971739, PMCID: PMC2993268, DOI: 10.2353/ajpath.2010.100199.Peer-Reviewed Original ResearchConceptsUnilateral ureteral obstructionAcute tubular necrosisEpithelial cellsRenal tubular epithelial cellsMurine kidneyIschemia/reperfusionMeasurement of fibrosisDistal nephron segmentsRecruitment of macrophagesWild-type miceInflammatory gene expressionTubular epithelial cellsDe novo expressionHuman biopsy specimensRenal injuryTubular necrosisUreteral obstructionWT miceVascular injuryHistological damageBiopsy specimensCortical tubulesDeficient miceMacrophage recruitmentTissue injury
2009
Deletion of the Met receptor in the collecting duct decreases renal repair following ureteral obstruction
Ma H, Saenko M, Opuko A, Togawa A, Soda K, Marlier A, Moeckel GW, Cantley LG, Ishibe S. Deletion of the Met receptor in the collecting duct decreases renal repair following ureteral obstruction. Kidney International 2009, 76: 868-876. PMID: 19675527, DOI: 10.1038/ki.2009.304.Peer-Reviewed Original ResearchConceptsUreteral obstructionFibrotic responseKnockout miceMet receptorAcute tubular necrosisPlasminogen activator inhibitor-1Unilateral ureteral obstructionTubular cell proliferationActivator inhibitor-1Conditional knockout miceHepatocyte growth factorKidney injuryRenal injuryTubular necrosisFunctional recoveryInterstitial fibrosisCre miceRenal repairNephron injuryControl littermatesObstructionGrowth factorMiceInhibitor-1InjuryResolution of renal inflammation: a new role for NF-κB1 (p50) in inflammatory kidney diseases
Panzer U, Steinmetz OM, Turner JE, Meyer-Schwesinger C, von Ruffer C, Meyer TN, Zahner G, Gómez-Guerrero C, Schmid RM, Helmchen U, Moeckel GW, Wolf G, Stahl RA, Thaiss F. Resolution of renal inflammation: a new role for NF-κB1 (p50) in inflammatory kidney diseases. American Journal Of Physiology. Renal Physiology 2009, 297: f429-f439. PMID: 19458123, DOI: 10.1152/ajprenal.90435.2008.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAcute DiseaseAnimalsAntilymphocyte SerumBlotting, SouthwesternCells, CulturedChemokinesDisease Models, AnimalEndothelial CellsGlomerulonephritisImmunohistochemistryKidney GlomerulusLipopolysaccharidesMaleMiceMice, Inbred C57BLMice, KnockoutNephritisNF-kappa B p50 SubunitNF-kappa B p52 SubunitProtein MultimerizationRatsRats, WistarRemission, SpontaneousTime FactorsTranscription Factor RelATranscription Factor RelBConceptsNF-kappaBRenal inflammationTissue injuryNF-kappaB p50 knockout miceRenal inflammatory cell infiltrationHighest chemokine expressionP50 knockout miceRenal tissue injuryResolution of LPSGlomerular immune injuryInflammatory kidney diseasesInflammatory cell infiltrationRenal inflammatory diseaseProinflammatory gene expressionModel of glomerulonephritisTranscription factor NF-kappaBResolution periodImmune injuryRenal diseaseChemokine expressionAcute nephritisKidney diseaseCell infiltrationInflammatory diseasesInflammatory process
2008
β1 integrin expression by podocytes is required to maintain glomerular structural integrity
Pozzi A, Jarad G, Moeckel GW, Coffa S, Zhang X, Gewin L, Eremina V, Hudson BG, Borza DB, Harris RC, Holzman LB, Phillips CL, Fassler R, Quaggin SE, Miner JH, Zent R. β1 integrin expression by podocytes is required to maintain glomerular structural integrity. Developmental Biology 2008, 316: 288-301. PMID: 18328474, PMCID: PMC2396524, DOI: 10.1016/j.ydbio.2008.01.022.Peer-Reviewed Original ResearchConceptsEnd-stage renal failureStage renal failureGlomerular structural integrityWeeks of agePodocin-cre miceGlomerular basement membraneGlomerular filtration barrier integrityNormal glomerular basement membraneExpression of beta1Renal failureGlomerular pathologyFiltration barrier integrityProgressive podocyte lossPodocyte lossGlomerular filtrationΒ1 integrin expressionBarrier integrityPodocyte abnormalitiesHeteromeric receptorsCapillary loopsGlomerular capillary formationMiceIntegrin expressionExtracellular matrixPodocytesFibrocystin/Polyductin Modulates Renal Tubular Formation by Regulating Polycystin-2 Expression and Function
Kim I, Fu Y, Hui K, Moeckel G, Mai W, Li C, Liang D, Zhao P, Ma J, Chen XZ, George AL, Coffey RJ, Feng ZP, Wu G. Fibrocystin/Polyductin Modulates Renal Tubular Formation by Regulating Polycystin-2 Expression and Function. Journal Of The American Society Of Nephrology 2008, 19: 455-468. PMID: 18235088, PMCID: PMC2391052, DOI: 10.1681/asn.2007070770.Peer-Reviewed Original ResearchConceptsFibrocystin/polyductinPC2 channel activityRenal cystic phenotypeGene-targeted mutationPolycystic kidney diseaseCultured renal epithelial cellsAutosomal recessive polycystic kidney diseaseHuman autosomal recessive polycystic kidney diseaseCommon molecular pathwaysEpithelial cellsRecessive polycystic kidney diseaseRenal epithelial cellsAberrant ciliogenesisKidney diseasePolycystin-2Polycystin-2 expressionPrimary ciliaCystic phenotypeSingle mutationMolecular pathwaysGenetic modifiersPhenotypic characteristicsMutationsMolecular interactionsAutosomal dominant polycystic kidney disease