2018
Pathologic Perspectives on Acute Tubular Injury Assessment in the Kidney Biopsy
Moeckel GW. Pathologic Perspectives on Acute Tubular Injury Assessment in the Kidney Biopsy. Seminars In Nephrology 2018, 38: 21-30. PMID: 29291758, DOI: 10.1016/j.semnephrol.2017.09.003.Peer-Reviewed Original ResearchConceptsAcute tubular injuryKidney biopsy analysisRenal pathology laboratoryTissue injury markersClinical time courseCell injury pathwaysTime courseNephrologists' managementInjury markersTubular injuryTubular lesionsKidney biopsyPathophysiological mechanismsTreatment modalitiesPatient managementDrug choiceEtiologic mechanismsInjury pathwaysToxic injuryPathologic perspectiveToxic etiologyBiopsy samplesClinical practiceBiopsy analysisPathology practice
2017
MIF-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
2014
Renalase 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
Met 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 activationHypertonic stress and cell death. Focus on “Multiple cell death pathways are independently activated by lethal hypertonicity in renal epithelial cells”
Moeckel GW. Hypertonic stress and cell death. Focus on “Multiple cell death pathways are independently activated by lethal hypertonicity in renal epithelial cells”. American Journal Of Physiology - Cell Physiology 2013, 305: c1009-c1010. PMID: 24005043, DOI: 10.1152/ajpcell.00263.2013.Peer-Reviewed Original ResearchChitinase-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
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
Hypertonicity-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
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-1InjuryDistinct Roles for Basal and Induced COX-2 in Podocyte Injury
Cheng H, Fan X, Guan Y, Moeckel GW, Zent R, Harris RC. Distinct Roles for Basal and Induced COX-2 in Podocyte Injury. Journal Of The American Society Of Nephrology 2009, 20: 1953-1962. PMID: 19643929, PMCID: PMC2736764, DOI: 10.1681/asn.2009010039.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminuriaAnimalsAntibiotics, AntineoplasticApoptosisCell AdhesionCell Line, TransformedCell SurvivalCyclooxygenase 2DinoprostoneDoxorubicinGlomerulonephritisMaleMiceMice, Inbred StrainsMice, TransgenicPodocytesPuromycinReceptors, Prostaglandin EReceptors, ThromboxaneRNA, MessengerThromboxanesConceptsCyclooxygenase-2Thromboxane receptorCOX-2 knockout miceSelective deletionCOX-2 deletionInduced COX-2Receptor subtype 4COX-2 metabolitesFoot process effacementGlomerular injuryPodocyte injuryProstanoid receptorsAttenuated albuminuriaWild-type podocytesSubtype 4Transgenic miceProcess effacementTP antagonistPodocyte survivalInjuryMore prostaglandinsGenetic deletionMicePodocytesGreater expression
2008
NFATc1 Identifies a Population of Proximal Tubule Cell Progenitors
Langworthy M, Zhou B, de Caestecker M, Moeckel G, Baldwin HS. NFATc1 Identifies a Population of Proximal Tubule Cell Progenitors. Journal Of The American Society Of Nephrology 2008, 20: 311-321. PMID: 19118153, PMCID: PMC2637056, DOI: 10.1681/asn.2008010094.Peer-Reviewed Original ResearchConceptsProximal tubular cell injuryBALB/c miceAcute kidney injuryTubular cell injuryWild-type miceProximal tubule segmentsKidney injurySerum creatinineCalcineurin inhibitorsC miceSustained injuryNFATc1 activityPTC proliferationCell injuryProximal tubulesNFATc1 expressionSevere injuriesTubule cellsInjuryMercuric chlorideEpithelial regenerationNephron segmentsCyclosporin AMiceTubule segmentsApoptosis of the Thick Ascending Limb Results in Acute Kidney Injury
Srichai MB, Hao C, Davis L, Golovin A, Zhao M, Moeckel G, Dunn S, Bulus N, Harris RC, Zent R, Breyer MD. Apoptosis of the Thick Ascending Limb Results in Acute Kidney Injury. Journal Of The American Society Of Nephrology 2008, 19: 1538-1546. PMID: 18495962, PMCID: PMC2488270, DOI: 10.1681/asn.2007101101.Peer-Reviewed Original ResearchConceptsAcute kidney injuryKidney injuryToxin-induced acute kidney injurySevere acute kidney injuryNovel transgenic mouse modelAdministration of gancyclovirIschemia/reperfusionBlood urea nitrogenTransgenic mouse modelToxin-induced injuryThick ascending limbHerpes simplex virus 1 thymidine kinase geneCreatinine levelsNeutrophil infiltrationAcute injuryControl miceInjury resultsMouse modelTransgenic miceUrea nitrogenProximal tubulesTAL cellsAscending limbInjuryTubular segments
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