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-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 talin1
2013
NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy
Knauf F, Asplin JR, Granja I, Schmidt IM, Moeckel GW, David RJ, Flavell RA, Aronson PS. NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy. Kidney International 2013, 84: 895-901. PMID: 23739234, PMCID: PMC3772982, DOI: 10.1038/ki.2013.207.Peer-Reviewed Original ResearchConceptsProgressive renal failureRenal failureCalcium oxalate crystal depositionCrystal-associated diseasesOverproduction of oxalateWild-type miceHigh-oxalate dietNephropathy resultsOxalate nephropathyRenal histologyKidney diseaseOxalate dietInflammatory responseNALP3 expressionDietary oxalateIntestinal oxalateOxalate homeostasisSoluble oxalateNephropathyCrystal depositionMiceMultiple disordersNALP3DietInflammationA 7-year-old boy with renal insufficiency and proteinuria after stem cell transplant for T-cell acute lymphoblastic leukemia
Goodwin JE, Palmer M, Pashankar F, Tufro A, Moeckel G. A 7-year-old boy with renal insufficiency and proteinuria after stem cell transplant for T-cell acute lymphoblastic leukemia. Clinical Nephrology 2013, 82: 205-210. PMID: 23391318, PMCID: PMC6990651, DOI: 10.5414/cn107767.Peer-Reviewed Original ResearchConceptsStem cell transplantHematopoietic stem cell transplantCell transplantRenal insufficiencyKidney biopsyPediatric patientsNephrotic syndromeExtensive foot process effacementAbnormal lymphocyte responsesT-cell acute lymphoblastic leukemiaChronic kidney diseaseChronic interstitial nephritisAcute lymphoblastic leukemiaPre-conditioning regimensFoot process effacementHost diseaseImmunosuppressive therapyRenal failureInterstitial nephritisLymphocyte responsesCommon sequelaeInterstitial infiltratesProphylactic medicationKidney diseaseLikely multifactorial
2012
Role of dynamin, synaptojanin, and endophilin in podocyte foot processes
Soda K, Balkin DM, Ferguson SM, Paradise S, Milosevic I, Giovedi S, Volpicelli-Daley L, Tian X, Wu Y, Ma H, Son SH, Zheng R, Moeckel G, Cremona O, Holzman LB, De Camilli P, Ishibe S. Role of dynamin, synaptojanin, and endophilin in podocyte foot processes. Journal Of Clinical Investigation 2012, 122: 4401-4411. PMID: 23187129, PMCID: PMC3533561, DOI: 10.1172/jci65289.Peer-Reviewed Original ResearchConceptsRole of dynaminNormal embryonic developmentFiltration barrierSynaptic vesicle recyclingFoot process formationKidney filtration barrierGlomerular filtration barrierNeuronal synapse developmentDynamin's roleEndophilin 3Actin cytoskeletonActin dynamicsFunctional partnersDynamin 1Endophilin-1Embryonic developmentVesicle recyclingProtein networkKidney's glomerular filtration barrierSynapse developmentDynaminPodocyte foot processesNeuronal synapsesSynaptojaninEndophilinAcute Podocyte Vascular Endothelial Growth Factor (VEGF-A) Knockdown Disrupts alphaVbeta3 Integrin Signaling in the Glomerulus
Veron D, Villegas G, Aggarwal PK, Bertuccio C, Jimenez J, Velazquez H, Reidy K, Abrahamson DR, Moeckel G, Kashgarian M, Tufro A. Acute Podocyte Vascular Endothelial Growth Factor (VEGF-A) Knockdown Disrupts alphaVbeta3 Integrin Signaling in the Glomerulus. PLOS ONE 2012, 7: e40589. PMID: 22808199, PMCID: PMC3396653, DOI: 10.1371/journal.pone.0040589.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlood PressureCells, CulturedDown-RegulationDoxycyclineEndotheliumFibronectinsGene Knockdown TechniquesIntegrin alphaVbeta3MiceModels, AnimalNeuropilin-1PhenotypePodocytesProtein BindingProteinuriaRenal InsufficiencyRNA, Small InterferingSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsAcute renal failureVEGF receptor 2Renal failureEndothelial cell swellingPodocyte VEGFUrine VEGFGlomerular filtration barrierLocal injuryPodocyte effacementGlomerular ultrastructureAdult miceDoxycycline exposureReceptor 2Knockdown micePodocyte cell lineControl valuesGlomeruliNeuropilin-1MiceVEGFProtein levelsCell swellingVEGF knockdownProteinuriaFiltration barrier
2010
Hematuria and Decreased Kidney Function as Initial Signs of Acute B-Cell Lymphoblastic Leukemia
Seo-Mayer P, Kenney B, McNamara J, Stein J, Moeckel GW. Hematuria and Decreased Kidney Function as Initial Signs of Acute B-Cell Lymphoblastic Leukemia. American Journal Of Kidney Diseases 2010, 56: 1001-1005. PMID: 20599308, DOI: 10.1053/j.ajkd.2010.03.029.Peer-Reviewed Original ResearchConceptsAcute lymphoblastic leukemiaKidney biopsy specimenKidney functionLymphoblastic leukemiaAcute B-cell lymphoblastic leukemiaSmall round blue cellsB-cell lymphoblastic leukemiaInitial presenting signRound blue cellsExtensive retroperitoneal lymphadenopathySignificant nuclear atypiaInduction chemotherapyInitial manifestationRetroperitoneal lymphadenopathyBilateral nephromegalyPresenting signImmunohistochemical workupInterstitial infiltratesBiopsy specimenNuclear atypiaComputed tomographyPositive stainingUnusual caseTerminal deoxynucleotidyl transferaseInitial signs