2017
Histones and Neutrophil Extracellular Traps Enhance Tubular Necrosis and Remote Organ Injury in Ischemic AKI
Nakazawa D, Kumar SV, Marschner J, Desai J, Holderied A, Rath L, Kraft F, Lei Y, Fukasawa Y, Moeckel GW, Angelotti ML, Liapis H, Anders HJ. Histones and Neutrophil Extracellular Traps Enhance Tubular Necrosis and Remote Organ Injury in Ischemic AKI. Journal Of The American Society Of Nephrology 2017, 28: 1753-1768. PMID: 28073931, PMCID: PMC5461800, DOI: 10.1681/asn.2016080925.Peer-Reviewed Original ResearchConceptsNeutrophil extracellular trap formationExtracellular trap formationNeutrophil extracellular trapsTubular necrosisExtracellular trapsCell necrosisTubular epithelial cell deathTubular epithelial cell necrosisRemote organ dysfunctionRemote organ injuryRemote organ damageRenal ischemic injuryTubular cell necrosisIschemia-reperfusion injuryRemote tissue injuryAdditive protective effectEpithelial cell necrosisTUNEL-positive cellsEpithelial cell deathNovel molecular targetsTrap formationIschemic AKISevere AKIKidney injuryMultiorgan dysfunction
2015
Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in Podocytes
Hassan H, Tian X, Inoue K, Chai N, Liu C, Soda K, Moeckel G, Tufro A, Lee AH, Somlo S, Fedeles S, Ishibe S. Essential Role of X-Box Binding Protein-1 during Endoplasmic Reticulum Stress in Podocytes. Journal Of The American Society Of Nephrology 2015, 27: 1055-1065. PMID: 26303067, PMCID: PMC4814187, DOI: 10.1681/asn.2015020191.Peer-Reviewed Original ResearchConceptsX-box binding protein 1Endoplasmic reticulum stress responseEndoplasmic reticulum stressGlomerular filtration barrierPodocyte injuryReticulum stress responseBinding protein 1Reticulum stressProtein 1Filtration barrierFoot process effacementProgressive albuminuriaMouse modelProcess effacementUnfolded protein response pathwayEpithelial cellsNormal glomerular filtration barrierProtein response pathwayEndoplasmic reticulumPodocytesGenetic inactivationXBP1 pathwayInjuryJNK pathwayStress response
2014
GM-CSF Promotes Macrophage Alternative Activation after Renal Ischemia/Reperfusion Injury
Huen SC, Huynh L, Marlier A, Lee Y, Moeckel GW, Cantley LG. GM-CSF Promotes Macrophage Alternative Activation after Renal Ischemia/Reperfusion Injury. Journal Of The American Society Of Nephrology 2014, 26: 1334-1345. PMID: 25388222, PMCID: PMC4446881, DOI: 10.1681/asn.2014060612.Peer-Reviewed Original ResearchMeSH KeywordsAcute Kidney InjuryAnalysis of VarianceAnimalsBlotting, WesternCell ProliferationCells, CulturedDisease Models, AnimalGene Expression RegulationGranulocyte-Macrophage Colony-Stimulating FactorImmunohistochemistryKidney Tubules, ProximalMacrophage ActivationMaleMiceMice, Inbred C57BLMultivariate AnalysisPhenotypeRandom AllocationReal-Time Polymerase Chain ReactionReperfusion InjurySignal TransductionUp-RegulationConceptsIschemia/reperfusion injuryMacrophage alternative activationBone marrow-derived macrophagesAlternative activationMarrow-derived macrophagesTubular cellsGM-CSFReperfusion injuryReparative phenotypeTubular proliferationKidney ischemia/reperfusion injuryRenal ischemia/reperfusion injuryMouse proximal tubule cellsInitial kidney damageRepair phaseProximal tubule cellsTubular factorsIschemic injuryKidney damageProinflammatory macrophagesRenal repairMacrophage activationTubule cellsPharmacologic inhibitionMacrophagesRole of medullary progenitor cells in epithelial cell migration and proliferation
Chen D, Chen Z, Zhang Y, Park C, Al-Omari A, Moeckel GW. Role of medullary progenitor cells in epithelial cell migration and proliferation. American Journal Of Physiology. Renal Physiology 2014, 307: f64-f74. PMID: 24808539, PMCID: PMC4080159, DOI: 10.1152/ajprenal.00547.2013.Peer-Reviewed Original ResearchConceptsProgenitor cellsEpithelial cell migrationSide populationInterstitial cell lineEpithelial cellsBone marrow-derived stem cellsCell migrationMarrow-derived stem cellsInjury repairMedullary interstitiumDuct cellsInner medullaCell proliferationCell linesProliferationTubule formationStem cellsInterstitial progenitor cellsDifferentiation mediumCellsPhenotypic characteristicsCritical roleIMCD3 cellsPGE2CXCR4Loss 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-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 talin1
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 maturationAlloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-&kgr;B Signaling in Endothelial Cells
Jane-wit D, Manes TD, Yi T, Qin L, Clark P, Kirkiles-Smith NC, Abrahimi P, Devalliere J, Moeckel G, Kulkarni S, Tellides G, Pober JS. Alloantibody and Complement Promote T Cell–Mediated Cardiac Allograft Vasculopathy Through Noncanonical Nuclear Factor-&kgr;B Signaling in Endothelial Cells. Circulation 2013, 128: 2504-2516. PMID: 24045046, PMCID: PMC3885874, DOI: 10.1161/circulationaha.113.002972.Peer-Reviewed Original ResearchConceptsCardiac allograft vasculopathyPanel reactive antibodyNuclear factor-κB signalingFactor-κB signalingAllograft vasculopathyT cellsEndothelial cellsMembrane attack complexAlloreactive T cell activationChronic antibody-mediated rejectionNoncanonical nuclear factorProinflammatory gene programAntibody-mediated rejectionDonor-specific antibodiesGraft endothelial cellsLate allograft lossAlloreactive T cellsAllogeneic endothelial cellsT cell activationAttack complexHuman T cellsAllograft lossHeart transplantationTransplantation patientsLesion pathogenesisChitinase-Like Protein Brp-39/YKL-40 Modulates the Renal Response to Ischemic Injury and Predicts Delayed Allograft Function
Schmidt IM, Hall IE, Kale S, Lee S, He CH, Lee Y, Chupp GL, Moeckel GW, Lee CG, Elias JA, Parikh CR, Cantley LG. Chitinase-Like Protein Brp-39/YKL-40 Modulates the Renal Response to Ischemic Injury and Predicts Delayed Allograft Function. Journal Of The American Society Of Nephrology 2013, 24: 309-319. PMID: 23291472, PMCID: PMC3559482, DOI: 10.1681/asn.2012060579.Peer-Reviewed Original ResearchMeSH KeywordsAdipokinesAnimalsApoptosisBiomarkersCells, CulturedChitinase-3-Like Protein 1Delayed Graft FunctionDisease Models, AnimalEpithelial CellsGlycoproteinsHumansKidneyKidney TransplantationLectinsMacrophagesMaleMiceMice, Inbred C57BLPhosphatidylinositol 3-KinasesPredictive Value of TestsProto-Oncogene Proteins c-aktReperfusion InjurySignal TransductionTransplantation, HomologousConceptsBRP-39/YKLGraft functionKidney injuryYKL-40Reparative responseDeceased donor kidney transplantationKidney ischemia/reperfusionHours of transplantImmediate graft functionDelayed graft functionTubular cell deathIschemia/reperfusionDegree of injuryAllograft functionCell apoptotic deathKidney hypoperfusionKidney transplantationSystemic hypotensionRenal failureIschemic injuryRenal ischemiaRenal responseUrinary levelsBRP-39Activation of Akt
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 synapsesSynaptojaninEndophilinAcute Podocyte Vascular Endothelial Growth Factor (VEGF-A) Knockdown Disrupts alphaVbeta3 Integrin Signaling in the Glomerulus
Veron D, Villegas G, Aggarwal PK, Bertuccio C, Jimenez J, Velazquez H, Reidy K, Abrahamson DR, Moeckel G, Kashgarian M, Tufro A. Acute Podocyte Vascular Endothelial Growth Factor (VEGF-A) Knockdown Disrupts alphaVbeta3 Integrin Signaling in the Glomerulus. PLOS ONE 2012, 7: e40589. PMID: 22808199, PMCID: PMC3396653, DOI: 10.1371/journal.pone.0040589.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PressureCells, CulturedDown-RegulationDoxycyclineEndotheliumFibronectinsGene Knockdown TechniquesIntegrin alphaVbeta3MiceModels, AnimalNeuropilin-1PhenotypePodocytesProtein BindingProteinuriaRenal InsufficiencyRNA, Small InterferingSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsAcute renal failureVEGF receptor 2Renal failureEndothelial cell swellingPodocyte VEGFUrine VEGFGlomerular filtration barrierLocal injuryPodocyte effacementGlomerular ultrastructureAdult miceDoxycycline exposureReceptor 2Knockdown micePodocyte cell lineControl valuesGlomeruliNeuropilin-1MiceVEGFProtein levelsCell swellingVEGF knockdownProteinuriaFiltration barrier
2011
Podocyte COX-2 Exacerbates Diabetic Nephropathy by Increasing Podocyte (Pro)renin Receptor Expression
Cheng H, Fan X, Moeckel GW, Harris RC. Podocyte COX-2 Exacerbates Diabetic Nephropathy by Increasing Podocyte (Pro)renin Receptor Expression. Journal Of The American Society Of Nephrology 2011, 22: 1240-1251. PMID: 21737546, PMCID: PMC3137572, DOI: 10.1681/asn.2010111149.Peer-Reviewed Original ResearchConceptsCOX-2 transgenic miceDiabetic nephropathyFoot process effacementCOX-2Transgenic miceGlomerular injuryReceptor expressionHigh glucoseRenin-angiotensin systemMesangial matrix expansionCOX-2 inhibitionWild-type miceCOX-2 inhibitorsCyclooxygenase-2 expressionGlomerular basement membraneStreptozotocin modelProgressive albuminuriaSegmental thickeningMesangial expansionDiabetic mellitusCell injuryAnimal modelsInjuryIncreased expressionNephropathy
2010
TGF-β Receptor Deletion in the Renal Collecting System Exacerbates Fibrosis
Gewin L, Bulus N, Mernaugh G, Moeckel G, Harris RC, Moses HL, Pozzi A, Zent R. TGF-β Receptor Deletion in the Renal Collecting System Exacerbates Fibrosis. Journal Of The American Society Of Nephrology 2010, 21: 1334-1343. PMID: 20576806, PMCID: PMC2938601, DOI: 10.1681/asn.2010020147.Peer-Reviewed Original ResearchConceptsRenal collecting systemTGF-beta signalingRenal fibrosisReceptor deletionCollecting systemTGF-beta type II receptorUnilateral ureteral obstructionReceptor-mediated functionsRenal interstitial fibroblastsTGF-beta activationType II receptorParadoxic increaseUreteral obstructionII receptorsInterstitial fibroblastsInterstitial cellsFibrosisDuct cellsCollagen synthesisUreteric bud developmentInjuryMiceMatrix productionEnhanced levelsSignalingHypertonicity-induced Mitochondrial Membrane Permeability in Renal Medullary Interstitial Cells: Protective Role of Osmolytes
Zhang L, Chen D, Chen Z, Moeckel GW. Hypertonicity-induced Mitochondrial Membrane Permeability in Renal Medullary Interstitial Cells: Protective Role of Osmolytes. Cellular Physiology And Biochemistry 2010, 25: 753-760. PMID: 20511721, PMCID: PMC3030460, DOI: 10.1159/000315095.Peer-Reviewed Original ResearchConceptsPermeability transition poreHypertonicity-induced apoptosisOrganic osmolytesCytochrome cDelta psiFluorescence probe JC-1Cell deathMitochondrial membrane permeabilityMitochondrial membrane potentialHypertonic culture conditionsMajor organic osmolytesHypertonicity-induced changesHyperosmotic stressProtein abundanceMolecular mechanismsApoptotic pathwayTransition poreJC-1OsmolytesProapoptotic BaxCytoplasmApoptosisKidney cellsMembrane potentialImmunofluorescence labeling
2009
Resolution 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
Fibrocystin/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
2006
Glomerular injury is exacerbated in diabetic integrin α1-null mice
Zent R, Yan X, Su Y, Hudson B, Borza D, Moeckel G, Qi Z, Sado Y, Breyer M, Voziyan P, Pozzi A. Glomerular injury is exacerbated in diabetic integrin α1-null mice. Kidney International 2006, 70: 460-470. PMID: 16775606, DOI: 10.1038/sj.ki.5000359.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBasement MembraneCell DivisionCell MovementCells, CulturedCollagen Type IVDiabetes Mellitus, ExperimentalDiabetic NephropathiesDisease Models, AnimalGlomerular Filtration RateGlucoseGlycation End Products, AdvancedIntegrin alpha1Integrin alpha1beta1MaleMesangial CellsMiceMice, Inbred BALB CMice, KnockoutOxidative StressReactive Oxygen SpeciesConceptsGlomerular filtration rateWild-type miceDiabetic wild-type miceDiabetic nephropathyGlomerular injuryCollagen depositionMesangial cellsGlomerular basement membrane thickeningCollagen IVGlomerular collagen IVIntegrin alpha1-null miceNon-diabetic miceIntegrin α1-null miceBasement membrane thickeningDiabetic mutant mouseGlomerular collagen depositionROS productionCollagen IV productionSTZ injectionWeek 24Renal diseaseGlomerular depositionWeek 36Week 12Filtration rate
2003
COX2 Activity Promotes Organic Osmolyte Accumulation and Adaptation of Renal Medullary Interstitial Cells to Hypertonic Stress*
Moeckel GW, Zhang L, Fogo AB, Hao CM, Pozzi A, Breyer MD. COX2 Activity Promotes Organic Osmolyte Accumulation and Adaptation of Renal Medullary Interstitial Cells to Hypertonic Stress*. Journal Of Biological Chemistry 2003, 278: 19352-19357. PMID: 12637551, DOI: 10.1074/jbc.m302209200.Peer-Reviewed Original ResearchMeSH KeywordsAdaptation, PhysiologicalAldehyde ReductaseAnimalsApoptosisBetaineCaspase 3CaspasesCell SurvivalCells, CulturedCyclooxygenase 2Cyclooxygenase 2 InhibitorsCyclooxygenase InhibitorsDehydrationDNA FragmentationGene ExpressionHeat-Shock ProteinsHypertonic SolutionsIn Situ Nick-End LabelingInositolIsoenzymesKidney MedullaMembrane ProteinsMiceMice, Inbred C57BLMice, KnockoutProstaglandin-Endoperoxide SynthasesRNA, MessengerSorbitolSymportersTritiumConceptsMedullary interstitial cellsRenal medullary interstitial cellsInterstitial cellsCOX2 activityCOX2 inhibitionReductase mRNA expressionCOX2-specific inhibitorsRenal cell survivalCell survivalAnalgesic nephropathyCOX2 inhibitorsRenal medullaMRNA expressionPmol/Sorbitol accumulationInner medullaOrganic osmolyte accumulationKidney inner medullaMedullaCell deathBetaine concentrationsHypertonic stressPresent studySurvivalInhibitors