2016
FAT1 mutations cause a glomerulotubular nephropathy
Gee HY, Sadowski CE, Aggarwal PK, Porath JD, Yakulov TA, Schueler M, Lovric S, Ashraf S, Braun DA, Halbritter J, Fang H, Airik R, Vega-Warner V, Cho KJ, Chan TA, Morris LG, ffrench-Constant C, Allen N, McNeill H, Büscher R, Kyrieleis H, Wallot M, Gaspert A, Kistler T, Milford DV, Saleem MA, Keng WT, Alexander SI, Valentini RP, Licht C, Teh JC, Bogdanovic R, Koziell A, Bierzynska A, Soliman NA, Otto EA, Lifton RP, Holzman LB, Sibinga NE, Walz G, Tufro A, Hildebrandt F. FAT1 mutations cause a glomerulotubular nephropathy. Nature Communications 2016, 7: 10822. PMID: 26905694, PMCID: PMC4770090, DOI: 10.1038/ncomms10822.Peer-Reviewed Original ResearchConceptsSteroid-resistant nephrotic syndromeChronic kidney diseaseKnockdown of Fat1Podocyte foot process effacementTubular cell functionRenal tubular cellsFoot process effacementNephrotic syndromeNeurological involvementKidney diseaseFAT1 mutationsDisease entityPodocyte-specific deletionTubular cellsTubular ectasiaProcess effacementCell functionDecreased migrationRac1/Cdc42PathogenesisFAT1Barrier developmentKnockdownRecessive mutationsHaematuria
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 miceNephropathyTubular Vascular Endothelial Growth Factor-A, Erythropoietin, and Medullary Vessels: A Trio Linked by Hypoxia
Tufro A. Tubular Vascular Endothelial Growth Factor-A, Erythropoietin, and Medullary Vessels: A Trio Linked by Hypoxia. Journal Of The American Society Of Nephrology 2014, 26: 997-998. PMID: 25385850, PMCID: PMC4413774, DOI: 10.1681/asn.2014101004.Peer-Reviewed Original ResearchPodocyte-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 mice
2013
Cholesterol Accumulation in Podocytes: A Potential Novel Targetable Pathway in Diabetic Nephropathy
Tufro A. Cholesterol Accumulation in Podocytes: A Potential Novel Targetable Pathway in Diabetic Nephropathy. Diabetes 2013, 62: 3661-3662. PMID: 24158993, PMCID: PMC3806593, DOI: 10.2337/db13-1167.Peer-Reviewed Original ResearchExcess Podocyte Semaphorin-3A Leads to Glomerular Disease Involving PlexinA1–Nephrin Interaction
Reidy KJ, Aggarwal PK, Jimenez JJ, Thomas DB, Veron D, Tufro A. Excess Podocyte Semaphorin-3A Leads to Glomerular Disease Involving PlexinA1–Nephrin Interaction. American Journal Of Pathology 2013, 183: 1156-1168. PMID: 23954273, PMCID: PMC3791681, DOI: 10.1016/j.ajpath.2013.06.022.Peer-Reviewed Original Research
2012
Acute 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
2011
Vascular Endothelial Growth Factor Receptor 2 Direct Interaction with Nephrin Links VEGF-A Signals to Actin in Kidney Podocytes*
Bertuccio C, Veron D, Aggarwal PK, Holzman L, Tufro A. Vascular Endothelial Growth Factor Receptor 2 Direct Interaction with Nephrin Links VEGF-A Signals to Actin in Kidney Podocytes*. Journal Of Biological Chemistry 2011, 286: 39933-39944. PMID: 21937443, PMCID: PMC3220571, DOI: 10.1074/jbc.m111.241620.Peer-Reviewed Original ResearchMeSH KeywordsActinsAdaptor Proteins, Signal TransducingAnimalsChlorocebus aethiopsCOS CellsMass SpectrometryMembrane ProteinsMiceMice, TransgenicMultiprotein ComplexesOncogene ProteinsPhosphorylationPodocytesProtein Structure, TertiarySignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsVEGF receptor 2Cytoplasmic domainTransmembrane protein nephrinBlot overlay experimentsSpecialized cell junctionsFoot process structurePodocyte actin cytoskeletonExtracellular cuesActin cytoskeletonGrowth factorMultiprotein interactionsTyrosine phosphorylationOverlay experimentsPodocyte cytoskeletonPodocyte foot processesCell junctionsPodocyte shapeCultured cellsKidney podocytesProtein nephrinSlit diaphragmDirect interactionCytoskeletonEpithelial cellsCultured podocytesPodocyte 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
2010
Induction of Podocyte VEGF164 Overexpression at Different Stages of Development Causes Congenital Nephrosis or Steroid-Resistant Nephrotic Syndrome
Veron D, Reidy K, Marlier A, Bertuccio C, Villegas G, Jimenez J, Kashgarian M, Tufro A. Induction of Podocyte VEGF164 Overexpression at Different Stages of Development Causes Congenital Nephrosis or Steroid-Resistant Nephrotic Syndrome. American Journal Of Pathology 2010, 177: 2225-2233. PMID: 20829436, PMCID: PMC2966782, DOI: 10.2353/ajpath.2010.091146.Peer-Reviewed Original ResearchConceptsNephrotic syndromePodocyte effacementTransgenic miceSteroid-resistant nephrotic syndromeEndothelial cellsSingle transgenic miceMultiple renal diseasesSwollen endothelial cellsCongenital nephrotic syndromeVascular endothelial growthInducible transgenic miceNormal endothelial cellsGlomerular filtration barrierRenal diseasePathogenic rolePodocyte lossMice expressMassive albuminuriaEndothelial growthCongenital nephrosisMinimal changesFoot processesMiceGlomerulomegalyAlbuminuriaOverexpression of VEGF-A in podocytes of adult mice causes glomerular disease
Veron D, Reidy KJ, Bertuccio C, Teichman J, Villegas G, Jimenez J, Shen W, Kopp JB, Thomas DB, Tufro A. Overexpression of VEGF-A in podocytes of adult mice causes glomerular disease. Kidney International 2010, 77: 989-999. PMID: 20375978, DOI: 10.1038/ki.2010.64.Peer-Reviewed Original ResearchMeSH KeywordsAge FactorsAnimalsAutocrine CommunicationDiabetic NephropathiesGenotypeGlomerular Basement MembraneKidney DiseasesMatrix Metalloproteinase 9Membrane ProteinsMiceMice, TransgenicParacrine CommunicationPhenotypePhosphorylationPodocytesProtein BindingProteinuriaSignal TransductionUp-RegulationVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-2ConceptsGlomerular diseaseAdult miceGlomerular basement membrane thickeningMurine diabetic nephropathyBasement membrane thickeningGlomerular endothelial cellsAdult transgenic miceOverexpression of VEGFExcessive VEGFDiabetic nephropathyGlomerular filtration barrierMesangial expansionPathogenic roleMetalloproteinase-9Functional abnormalitiesMembrane thickeningPodocyte effacementNephrin expressionReceptor 2Transgenic miceWhole kidneyGlomerular phenotypeEndothelial cellsParacrine VEGFVEGF
2009
Semaphorin3a regulates endothelial cell number and podocyte differentiation during glomerular development
Reidy KJ, Villegas G, Teichman J, Veron D, Shen W, Jimenez J, Thomas D, Tufro A. Semaphorin3a regulates endothelial cell number and podocyte differentiation during glomerular development. Development 2009, 136: 3979-3989. PMID: 19906865, PMCID: PMC2778745, DOI: 10.1242/dev.037267.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCell CountCell DifferentiationCell NucleusCoculture TechniquesEndothelial CellsFluorescent Antibody Technique, DirectFluorescent DyesGene DeletionGene Expression Regulation, DevelopmentalGriffoniaImmunohistochemistryIn Situ Nick-End LabelingIndolesKidney GlomerulusMiceMice, KnockoutMice, Mutant StrainsMice, TransgenicPlant LectinsPodocytesRatsRecombinant ProteinsSemaphorin-3AConceptsVascular patterningPodocyte differentiationNegative regulatorNormal glomerular filtration barrierGlomerular developmentEssential negative regulatorEndothelial cell survivalFunction mouse modelsTight regulationEndothelial cell apoptosisUreteric budMature podocytesVascular developmentCell survivalCrucial roleGuidance proteinsSlit diaphragmCell apoptosisGlomerular filtration barrierRegulatorFiltration barrierGlomerular endothelial cell apoptosisCell numberEndothelial cellsEndothelial cell number
2007
Semaphorin3a inhibits ureteric bud branching morphogenesis
Tufro A, Teichman J, Woda C, Villegas G. Semaphorin3a inhibits ureteric bud branching morphogenesis. Cells And Development 2007, 125: 558-568. PMID: 18249526, PMCID: PMC3992265, DOI: 10.1016/j.mod.2007.12.003.Peer-Reviewed Original ResearchConceptsUreteric budUreteric bud branchingAkt survival pathwayUreteric bud treeUreteric bud cellsAntisense morpholinoClass 3 semaphorinsVascular patterningMetanephric organ cultureFactor signalingMouse embryosNegative regulatorKidney developmentSurvival pathwaysGuidance proteinsNeurotrophic Factor SignalingSema3A effectBudsRenal epitheliumMorphogenesisBud cellsMutant miceRecombinant Sema3AGrowth factorSema3ASemaphorin3a disrupts podocyte foot processes causing acute proteinuria
Tapia R, Guan F, Gershin I, Teichman J, Villegas G, Tufro A. Semaphorin3a disrupts podocyte foot processes causing acute proteinuria. Kidney International 2007, 73: 733-740. PMID: 18075495, DOI: 10.1038/sj.ki.5002726.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsCytoskeletal ProteinsDown-RegulationGlomerular Basement MembraneGlomerular Filtration RateIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsMiceMice, Inbred StrainsPermeabilityPodocytesProteinuriaRecombinant ProteinsSemaphorin-3AVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2ConceptsPodocyte foot process effacementNephrotic range proteinuriaEndothelial cell damageVascular endothelial growth factorSlit diaphragm protein podocinFoot process effacementEndothelial growth factorReceptor 2 signalingVascular endothelial growth factor receptor 2 signalingAcute proteinuriaRange proteinuriaReceptor expressionVascular endothelial growth factor 165Process effacementBarrier homeostasisAdult mouse kidneyUltrastructural abnormalitiesSemaphorin3AEndothelial cellsCell damageGrowth factorMouse kidneyGuidance proteinsProteinuriaDownregulationCrosstalk between VEGF-A/VEGFR2 and GDNF/RET signaling pathways
Tufro A, Teichman J, Banu N, Villegas G. Crosstalk between VEGF-A/VEGFR2 and GDNF/RET signaling pathways. Biochemical And Biophysical Research Communications 2007, 358: 410-416. PMID: 17490619, DOI: 10.1016/j.bbrc.2007.04.146.Peer-Reviewed Original ResearchConceptsVascular endothelial growth factorCell proliferationEndothelial growth factorNeurotrophic factorGDNF/RETEmbryonic kidney explantsUreteric bud branchingUreteric bud cellsC-RetGrowth factorRT-PCRVEGFNovel cooperative interactionVEGFR2Branching morphogenesisRETVEGFR2 autophosphorylationGDNFKidney developmentBud cellsUreteric budAdditive effectMajor regulatorKidney explantsPhosphorylation
2006
Semaphorin 3C regulates endothelial cell function by increasing integrin activity
Banu N, Teichman J, Dunlap‐Brown M, Villegas G, Tufro A, Banu N, Teichman J, Dunlap‐Brown M, Villegas G, Tufro A. Semaphorin 3C regulates endothelial cell function by increasing integrin activity. The FASEB Journal 2006, 20: 2150-2152. PMID: 16940438, DOI: 10.1096/fj.05-5698fje.Peer-Reviewed Original ResearchConceptsSema 3CEndothelial cell functionDirectional migrationStarvation-induced apoptosisCell functionCapillary-like network formationCardiovascular patterningClass 3 semaphorinsIntegrin phosphorylationSerine phosphorylationCollagen I gelsVascular morphogenesisEndothelial cellsMouse glomerular endothelial cellsIntegrin activityGuidance proteinsEndothelial cell proliferationIntegrin inhibitionCaspase-3Cell proliferationSitu markerTube formationSemaphorin 3CPhosphorylationGrowth factorAutocrine class 3 semaphorin system regulates slit diaphragm proteins and podocyte survival
Guan F, Villegas G, Teichman J, Mundel P, Tufro A. Autocrine class 3 semaphorin system regulates slit diaphragm proteins and podocyte survival. Kidney International 2006, 69: 1564-1569. PMID: 16541019, DOI: 10.1038/sj.ki.5000313.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsApoptosisAutocrine CommunicationCells, CulturedCytoskeletal ProteinsDown-RegulationIntracellular Signaling Peptides and ProteinsKidney GlomerulusMembrane ProteinsMicePhosphorylationPodocytesProteinsProto-Oncogene Proteins c-aktReceptors, Cell SurfaceReceptors, ImmunologicSemaphorin-3ASemaphorinsConceptsReverse transcriptase-polymerase chain reactionClass 3 semaphorinsPodocyte survivalSlit diaphragm proteinsSema 3APodocyte apoptosisDiaphragm proteinsTranscriptase-polymerase chain reactionDifferentiated podocytesSema 3A.Activity markersAkt survival pathwayDifferentiated mouse podocytesSemaphorin 3ASemaphorin 3BGuidance proteinsMouse podocytesPodocytesMRNA levelsSurvival pathwaysUndetectable levelsChain reactionPlexin-A1SurvivalSemaphorin RegulationAutocrine VEGF-A system in podocytes regulates podocin and its interaction with CD2AP
Guan F, Villegas G, Teichman J, Mundel P, Tufro A. Autocrine VEGF-A system in podocytes regulates podocin and its interaction with CD2AP. American Journal Of Physiology. Renal Physiology 2006, 291: f422-f428. PMID: 16597608, DOI: 10.1152/ajprenal.00448.2005.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsC-Reactive ProteinCell DifferentiationCell LineCell SurvivalCytoskeletal ProteinsGene Expression RegulationIntracellular Signaling Peptides and ProteinsMembrane ProteinsMiceNerve Tissue ProteinsNeuropilin-2PodocytesProteinsProto-Oncogene Proteins c-aktReceptors, Vascular Endothelial Growth FactorRNA, MessengerSignal TransductionVascular Endothelial Growth Factor AVascular Endothelial Growth Factor Receptor-1Vascular Endothelial Growth Factor Receptor-2ConceptsWestern analysisAutocrine VEGFPodocyte VEGFGrowth factor signalingVEGFR2 mRNA levelsMRNA levelsEndothelial cell differentiationVascular endothelial growth factor signalingCompletion of developmentVascular patterningKidney morphogenesisFactor signalingPodocyte differentiationUndifferentiated podocytesLigand availabilityCell differentiationVEGFR2 phosphorylationDifferentiated conditionsImmortalized mouse podocytesProtein levelsProtein expressionMouse podocytesVEGFR2 mRNADifferentiated podocytesCD2AP
2005
Autocrine and paracrine functions of vascular endothelial growth factor (VEGF) in renal tubular epithelial cells
Villegas G, Lange-Sperandio B, Tufro A. Autocrine and paracrine functions of vascular endothelial growth factor (VEGF) in renal tubular epithelial cells. Kidney International 2005, 67: 449-457. PMID: 15673292, DOI: 10.1111/j.1523-1755.2005.67101.x.Peer-Reviewed Original Research