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 animals
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
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 miceNephropathyPodocyte-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
2009
Distinct 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
2007
Puromycin Induces Reversible Proteinuric Injury in Transgenic Mice Expressing Cyclooxygenase-2 in Podocytes
Jo YI, Cheng H, Wang S, Moeckel GW, Harris RC. Puromycin Induces Reversible Proteinuric Injury in Transgenic Mice Expressing Cyclooxygenase-2 in Podocytes. Nephron 2007, 107: e87-e94. PMID: 17890881, DOI: 10.1159/000108653.Peer-Reviewed Original ResearchConceptsCOX-2 expressionCOX-2-specific inhibitorsCOX-2 mRNATransgenic miceFoot process effacementDay 3COX-2Process effacementEndogenous COX-2 mRNAImmunoreactive COX-2Progressive renal diseaseCOX-2 overexpressionFoot process fusionCyclooxygenase-2 inhibitorRenal diseaseGlomerular injurySignificant albuminuriaCyclooxygenase-2Further injuryReal-time PCRDay 1Nephrin mRNADay 10AlbuminuriaMiceOverexpression of Cyclooxygenase-2 Predisposes to Podocyte Injury
Cheng H, Wang S, Jo YI, Hao CM, Zhang M, Fan X, Kennedy C, Breyer MD, Moeckel GW, Harris RC. Overexpression of Cyclooxygenase-2 Predisposes to Podocyte Injury. Journal Of The American Society Of Nephrology 2007, 18: 551-559. PMID: 17202413, DOI: 10.1681/asn.2006090990.Peer-Reviewed Original ResearchConceptsCOX-2 expressionBALB/c miceFoot process effacementTransgenic miceC micePodocyte injuryProcess effacementCOX-2 transgenic miceImmunoreactive COX-2 expressionCOX-2 mRNA expressionNephrin promoterLong-term treatmentCOX-2 overexpressionTransgenic mouse kidneyCyclooxygenase-2 expressionWild-type miceWild-type littermatesCOX-2 mRNARenal injuryRenal ablationAdriamycin nephropathyMore albuminuriaAdriamycin administrationFurther injuryCOX-2