2017
Rapamycin 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 model
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
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 expressionNephropathyPodocyte vascular endothelial growth factor (Vegf164) overexpression causes severe nodular glomerulosclerosis in a mouse model of type 1 diabetes
Veron D, Bertuccio CA, Marlier A, Reidy K, Garcia AM, Jimenez J, Velazquez H, Kashgarian M, Moeckel GW, Tufro A. Podocyte vascular endothelial growth factor (Vegf164) overexpression causes severe nodular glomerulosclerosis in a mouse model of type 1 diabetes. Diabetologia 2011, 54: 1227-1241. PMID: 21318407, PMCID: PMC3397150, DOI: 10.1007/s00125-010-2034-z.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternChromatography, High Pressure LiquidCreatinineDiabetes Mellitus, Type 1Diabetic NephropathiesDisease Models, AnimalEnzyme-Linked Immunosorbent AssayImmunohistochemistryMiceMice, TransgenicMicroscopy, Electron, TransmissionPodocytesPolymerase Chain ReactionSemaphorin-3ATandem Mass SpectrometryVascular Endothelial Growth Factor AConceptsDiabetic nephropathyNodular glomerulosclerosisDiabetic glomerulopathyMouse modelMassive proteinuriaExcessive vascular endothelial growth factorTransgenic miceStreptozotocin-induced mouse modelVascular endothelial growth factor overexpressionGlomerular basement membrane thickeningAdvanced diabetic glomerulopathyControl diabetic miceOnset of diabetesBasement membrane thickeningVascular endothelial growth factorType 1 diabetesGrowth factor overexpressionAdult transgenic miceEndothelial growth factorVEGF receptor 2Kimmelstiel-WilsonSystemic VEGFDiabetic micePathogenic roleRenal morphology
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
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 segmentsβ1 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 matrixPodocytes
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