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
2020
Kidney tissue hypoxia dictates T cell–mediated injury in murine lupus nephritis
Chen PM, Wilson PC, Shyer JA, Veselits M, Steach HR, Cui C, Moeckel G, Clark MR, Craft J. Kidney tissue hypoxia dictates T cell–mediated injury in murine lupus nephritis. Science Translational Medicine 2020, 12 PMID: 32269165, PMCID: PMC8055156, DOI: 10.1126/scitranslmed.aay1620.Peer-Reviewed Original ResearchConceptsHypoxia-inducible factor-1Lupus nephritisT cellsTissue hypoxiaT-cell-mediated injuryCell-mediated injuryHIF-1 blockadeKidney tissue hypoxiaSystemic lupus erythematosusHuman lupus nephritisMurine lupus nephritisRenal injuryAutoimmune injuryLupus erythematosusAutoimmune diseasesImmune cellsRenal tissueMurine modelTissue damageMore hypoxicNephritisInjuryLow oxygen tensionOxygen tensionFactor 1Polycystin 2 is increased in disease to protect against stress-induced cell death
Brill AL, Fischer TT, Walters JM, Marlier A, Sewanan LR, Wilson PC, Johnson EK, Moeckel G, Cantley LG, Campbell SG, Nerbonne JM, Chung HJ, Robert ME, Ehrlich BE. Polycystin 2 is increased in disease to protect against stress-induced cell death. Scientific Reports 2020, 10: 386. PMID: 31941974, PMCID: PMC6962458, DOI: 10.1038/s41598-019-57286-x.Peer-Reviewed Original ResearchConceptsPolycystin-2General cellular homeostasisCell deathStress-induced cell deathPathological cell deathAutosomal dominant polycystic kidney diseaseEndoplasmic reticulum membraneCellular homeostasisCellular stressPrimary ciliaUbiquitous expressionExpression changesCell stressReticulum membraneTransient receptor potential cation channelHuman diseasesMultiple tissuesEndogenous roleDominant polycystic kidney diseaseTissue typesCation channelsPolycystic kidney diseaseDifferent pathological statesMultiple diseasesKidney disease
2019
Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease
Landau SI, Guo X, Velazquez H, Torres R, Olson E, Garcia-Milian R, Moeckel GW, Desir GV, Safirstein R. Regulated necrosis and failed repair in cisplatin-induced chronic kidney disease. Kidney International 2019, 95: 797-814. PMID: 30904067, PMCID: PMC6543531, DOI: 10.1016/j.kint.2018.11.042.Peer-Reviewed Original ResearchConceptsChronic kidney diseaseKidney diseaseKidney injuryCisplatin-induced chronic kidney diseaseCisplatin-induced acute kidney injuryToll-like receptor 2Regulated necrosis pathwaysReversible kidney injuryAcute kidney injuryChronic kidney injuryProximal tubular damageKidney injury markersDoses of cisplatinEvidence of fibrosisMechanisms of progressionEffective chemotherapeutic agentWestern blot analysisFirst doseInjury markersIntraperitoneal cisplatinSignificant nephrotoxicityTubular damageKidney functionSecond doseCisplatin administration
2018
Semaphorin 7A in circulating regulatory T cells is increased in autosomal-dominant polycystic kidney disease and decreases with tolvaptan treatment
Lee Y, Blount KL, Dai F, Thompson S, Scher JK, Bitterman S, Droher M, Herzog EL, Moeckel G, Karihaloo A, Dahl NK. Semaphorin 7A in circulating regulatory T cells is increased in autosomal-dominant polycystic kidney disease and decreases with tolvaptan treatment. Clinical And Experimental Nephrology 2018, 22: 906-916. PMID: 29453607, DOI: 10.1007/s10157-018-1542-x.Peer-Reviewed Original ResearchConceptsPeripheral blood mononuclear cellsAutosomal dominant polycystic kidney diseaseEnd-stage renal diseaseRenal fibrosisSEMA7A expressionADPKD patientsTolvaptan treatmentPolycystic kidney diseaseKidney diseaseNumber of PBMCsExpression of SEMA7ASubsequent renal fibrosisMarkers of inflammationRegulatory T cellsADPKD kidneysBlood mononuclear cellsImmunomodulating proteinsRenal diseaseMononuclear cellsSmall kidneysKidney fibrosisLiver fibrosisRenal cystsSemaphorin 7AT cells
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 animalsRapamycin treatment dose‐dependently improves the cystic kidney in a new ADPKD mouse model via the mTORC1 and cell‐cycle‐associated CDK1/cyclin axis
Li A, Fan S, Xu Y, Meng J, Shen X, Mao J, Zhang L, Zhang X, Moeckel G, Wu D, Wu G, Liang C. Rapamycin treatment dose‐dependently improves the cystic kidney in a new ADPKD mouse model via the mTORC1 and cell‐cycle‐associated CDK1/cyclin axis. Journal Of Cellular And Molecular Medicine 2017, 21: 1619-1635. PMID: 28244683, PMCID: PMC5543471, DOI: 10.1111/jcmm.13091.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibiotics, AntineoplasticCDC2 Protein KinaseCell CycleCyclinsDose-Response Relationship, DrugFemaleFounder EffectGene Expression RegulationHumansIntegrasesKidneyMaleMiceMice, TransgenicMicrofilament ProteinsPolycystic Kidney, Autosomal DominantPromoter Regions, GeneticSignal TransductionSirolimusTOR Serine-Threonine KinasesTRPP Cation ChannelsConceptsAutosomal dominant polycystic kidney diseaseEnd-stage renal diseaseMouse modelCyclin-dependent kinase 1Kidney/body weight ratioPreclinical trialsVivo preclinical resultsBody weight ratioCre transgenic miceHigh-dose rapamycinStandardized animal modelHuman autosomal dominant polycystic kidney diseaseRapamycin (mTOR) inhibitor rapamycinDominant polycystic kidney diseaseMonths of ageOrthologous mouse modelConditional knockout miceDose-dependent mannerPolycystic kidney diseaseAberrant epithelial cell proliferationEpithelial cell proliferationNew molecular targetsADPKD therapyRenal functionADPKD mouse modelHistones 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
2016
Isoforms of Spectrin and Ankyrin Reflect the Functional Topography of the Mouse Kidney
Stankewich MC, Moeckel GW, Ji L, Ardito T, Morrow JS. Isoforms of Spectrin and Ankyrin Reflect the Functional Topography of the Mouse Kidney. PLOS ONE 2016, 11: e0142687. PMID: 26727517, PMCID: PMC4703142, DOI: 10.1371/journal.pone.0142687.Peer-Reviewed Original ResearchConceptsBowman's capsuleEndothelial cellsFunctional topographyThick ascending loopGlomerular endothelial cellsProximal tubule cellsCapillary endothelial cellsAscending loopDistal tubulesDistal nephronTubule cellsTubular segmentsKidneyRodent kidneyWestern blottingMouse kidneyImmuno-electron microscopyThick loopAnkyrin GMetabolite traffickingSpectrin scaffoldHenleNephronCapsulePodocytes
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 responseThree-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD
Torres R, Velazquez H, Chang JJ, Levene MJ, Moeckel G, Desir GV, Safirstein R. Three-Dimensional Morphology by Multiphoton Microscopy with Clearing in a Model of Cisplatin-Induced CKD. Journal Of The American Society Of Nephrology 2015, 27: 1102-1112. PMID: 26303068, PMCID: PMC4814184, DOI: 10.1681/asn.2015010079.Peer-Reviewed Original ResearchConceptsAtubular glomeruliGlomerular capsuleRole of fibrosisModel of cisplatinNew mouse modelUseful morphologic informationMultiphoton microscopyTraditional histologic methodsRenal diseaseCisplatin therapyGlomerular volumePathologic changesRenal sectionsCKDMouse modelCisplatin effectCisplatin exposureImportant causeMild increaseCuboidal cellsHistologic methodsMorphologic informationFibrosisTherapyGlomeruli
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 miceNephropathyGM-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-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
Mineralocorticoid Receptor Phosphorylation Regulates Ligand Binding and Renal Response to Volume Depletion and Hyperkalemia
Shibata S, Rinehart J, Zhang J, Moeckel G, Castañeda-Bueno M, Stiegler AL, Boggon TJ, Gamba G, Lifton RP. Mineralocorticoid Receptor Phosphorylation Regulates Ligand Binding and Renal Response to Volume Depletion and Hyperkalemia. Cell Metabolism 2013, 18: 660-671. PMID: 24206662, PMCID: PMC3909709, DOI: 10.1016/j.cmet.2013.10.005.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAngiotensin IIAnimalsChlorocebus aethiopsCOS CellsCytoplasmElectrolytesHumansHyperkalemiaKidneyLigandsMiceMolecular Sequence DataPhosphoprotein PhosphatasesPhosphorylationPhosphoserinePotassium, DietaryProtein Serine-Threonine KinasesProtein TransportRatsReceptors, MineralocorticoidSignal TransductionTranscriptional ActivationConceptsVolume depletionMineralocorticoid receptorAldosterone-dependent increaseHormone receptor activityNuclear hormone receptor activityMR activationRenal responseDistinct adaptive responsesAngiotensin IIDistal nephronCl reabsorptionHyperkalemiaMR ligand-binding domainReceptor activityApical proton pumpPlasma volumeReceptor bindingHomeostatic responseNuclear receptorsReceptor phosphorylationMet 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 activation