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 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 mechanismsThree-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 informationFibrosisTherapyGlomeruliEssential 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
2011
Podocyte 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
2008
Apoptosis 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
2005
Expression of Mediators of Renal Injury in the Remnant Kidney of ROP Mice Is Attenuated by Cyclooxygenase-2 Inhibition
Cheng H, Zhang M, Moeckel GW, Zhao Y, Wang S, Qi Z, Breyer MD, Harris RC. Expression of Mediators of Renal Injury in the Remnant Kidney of ROP Mice Is Attenuated by Cyclooxygenase-2 Inhibition. Nephron 2005, 101: e75-e85. PMID: 15995341, DOI: 10.1159/000086645.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsConnective Tissue Growth FactorCyclooxygenase 2 InhibitorsFibronectinsGlomerulosclerosis, Focal SegmentalImmediate-Early ProteinsIntercellular Signaling Peptides and ProteinsKidneyKidney TubulesMiceMice, Inbred StrainsNephrectomyProteinuriaProto-Oncogene Proteins c-metPyrazolesSulfonamidesTissue DistributionConceptsCyclooxygenase-2 inhibitionROP miceSC58236 treatmentRenal injuryRemnant kidneyImmunoreactive COX-2Immunoreactive TGF-beta1Selective COX-2 inhibitorsSystemic blood pressureConnective tissue growth factorSubtotal renal ablationRenal tubulointerstitial injuryExpression of mediatorsCOX-2 inhibitorsTissue growth factorCollagen IV mRNATubulointerstitial injuryBlood pressureRenal ablationSignificant albuminuriaCOX-2Macrophage markersMouse modelTGF-beta1Remnant group