2023
Profilin1 is required to prevent mitotic catastrophe in murine and human glomerular diseases
Tian X, Pedigo C, Li K, Ma X, Bunda P, Pell J, Lek A, Gu J, Zhang Y, Rangel P, Li W, Schwartze E, Nagata S, Lerner G, Perincheri S, Priyadarshini A, Zhao H, Lek M, Menon M, Fu R, Ishibe S. Profilin1 is required to prevent mitotic catastrophe in murine and human glomerular diseases. Journal Of Clinical Investigation 2023, 133: e171237. PMID: 37847555, PMCID: PMC10721156, DOI: 10.1172/jci171237.Peer-Reviewed Original ResearchConceptsProteinuric kidney diseaseKidney diseasePodocyte lossHuman glomerular diseasesMitotic catastrophePodocyte cell cycleSevere proteinuriaCell cycle reentryKidney failureGlomerular diseaseCell cycleKidney tissueG1/S checkpointUnsuccessful repairCyclin D1Glomerular integrityIrregular nucleiTissue-specific lossMouse podocytesPodocytesAltered expressionDiseaseCyclin B1Ribosome affinity purificationMultinucleated cells
2022
Cell Cycle and Senescence Regulation by Podocyte Histone Deacetylase 1 and 2
Rangel P, Cross E, Liu C, Pedigo C, Tian X, Gutiérrez-Calabrés E, Nagata S, Priyadarshini A, Lerner G, Bunda P, Perincheri S, Gu J, Zhao H, Wang Y, Inoue K, Ishibe S. Cell Cycle and Senescence Regulation by Podocyte Histone Deacetylase 1 and 2. Journal Of The American Society Of Nephrology 2022, 34: 433-450. PMID: 36414418, PMCID: PMC10103311, DOI: 10.1681/asn.2022050598.Peer-Reviewed Original ResearchConceptsCell cycle entryDNA damageSenescence-associated β-galactosidase activityDouble knockout miceRole of HDACsNormal glomerular filtration barrierAssociated phenotypesP21-mediated cell cycle arrestOpen chromatin conformationGlomerular filtration barrierSevere proteinuriaKidney failureProinflammatory cytokinesCell cycle regulationHistone deacetylase 1Cell cycle arrestKi67 expressionSustained DNA damagePodocyte lossIntact expressionMice leadsPodocyte-specific lossMatrix metalloproteinasesPodocyte detachmentProteinuriaCoronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction.
Peng X, Kim J, Gupta G, Agaronyan K, Mankowski MC, Korde A, Takyar SS, Shin HJ, Habet V, Voth S, Audia JP, Chang D, Liu X, Wang L, Cai Y, Tian X, Ishibe S, Kang MJ, Compton S, Wilen CB, Dela Cruz CS, Sharma L. Coronavirus Lung Infection Impairs Host Immunity against Secondary Bacterial Infection by Promoting Lysosomal Dysfunction. The Journal Of Immunology 2022, 209: 1314-1322. PMID: 36165196, PMCID: PMC9523490, DOI: 10.4049/jimmunol.2200198.Peer-Reviewed Original ResearchConceptsSARS-CoV-2Bacterial infectionsMouse modelCoronavirus infectionLysosomal dysfunctionMajor health care challengeLung immune cellsLung tissue damageSecondary bacterial infectionImpair host immunityIL-1β releaseHealth care challengesCell deathPyroptotic cell deathBacterial killing abilityIL-1βBacterial clearanceImmune cellsSecondary infectionHost immunityAlveolar macrophagesTissue damageΒ-coronavirusStructural cellsCare challenges
2021
Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection
Sharma L, Peng X, Qing H, Hilliard BK, Kim J, Swaminathan A, Tian J, Israni-Winger K, Zhang C, Habet V, Wang L, Gupta G, Tian X, Ma Y, Shin HJ, Kim SH, Kang MJ, Ishibe S, Young LH, Kotenko S, Compton S, Wilen CB, Wang A, Dela Cruz CS. Distinct Roles of Type I and Type III Interferons during a Native Murine β Coronavirus Lung Infection. Journal Of Virology 2021, 96: e01241-21. PMID: 34705554, PMCID: PMC8791255, DOI: 10.1128/jvi.01241-21.Peer-Reviewed Original ResearchConceptsType I interferonType III interferonsI interferonIII interferonsCoronavirus infectionInterferon deficiencyViral clearanceViral loadLung infectionType IHealthy young patientsImproved host survivalHost survivalRole of interferonMurine coronavirus infectionMajor health care threatViral burdenYounger patientsEarly diseaseIntranasal routeInterferon treatmentSublethal infectionEarly treatmentLethal infectionTissue injuryAMP-Kinase mediates regulation of glomerular volume and podocyte survival
Banu K, Lin Q, Basgen JM, Planoutene M, Wei C, Reghuvaran AC, Tian X, Shi H, Garzon F, Garzia A, Chun N, Cumpelik A, Santeusanio AD, Zhang W, Das B, Salem F, LI L, Ishibe S, Cantley LG, Kaufman L, Lemley KV, Ni Z, He JC, Murphy B, Menon MC. AMP-Kinase mediates regulation of glomerular volume and podocyte survival. JCI Insight 2021, 6: e150004. PMID: 34473647, PMCID: PMC8525649, DOI: 10.1172/jci.insight.150004.Peer-Reviewed Original ResearchAdenylate KinaseAdolescentAdultAgedAlbuminuriaAnimalsCell SizeCell SurvivalChildChild, PreschoolFemaleGene Knockdown TechniquesGlomerulonephritis, MembranousGlomerulosclerosis, Focal SegmentalHumansHypertrophyInfantKidney GlomerulusMaleMiceMicrofilament ProteinsMiddle AgedNephrectomyNephrosis, LipoidNephrotic SyndromePodocytesProportional Hazards ModelsProto-Oncogene Proteins c-fynYoung AdultProfibrotic mechanisms of DPP8 and DPP9 highly expressed in the proximal renal tubule epithelial cells
Zhang Y, Li K, Li Y, Zhao W, Wang L, Chen Z, Ma X, Yao T, Wang J, Dong W, Li X, Tian X, Fu R. Profibrotic mechanisms of DPP8 and DPP9 highly expressed in the proximal renal tubule epithelial cells. Pharmacological Research 2021, 169: 105630. PMID: 33932609, DOI: 10.1016/j.phrs.2021.105630.Peer-Reviewed Original ResearchMeSH KeywordsAdamantaneAnimalsBlotting, WesternCase-Control StudiesCell LineDipeptidasesDipeptidesDipeptidyl-Peptidases and Tripeptidyl-PeptidasesEpithelial-Mesenchymal TransitionFibrosisFluorescent Antibody TechniqueHumansKidney Tubules, ProximalMaleMiceMice, Inbred C57BLReal-Time Polymerase Chain ReactionRenal Insufficiency, ChronicConceptsTubulointerstitial fibrosisTubule epithelial cellsCKD patientsUUO miceHK-2 cell modelChronic kidney disease patientsTGF-β1/Smad signalingUnilateral ureteral obstruction animal modelEpithelial cellsKidney disease patientsHealthy control subjectsKidney biopsy specimensProximal tubule epithelial cellsRenal tubule epithelial cellsRenal proximal tubule epithelial cellsHK-2 cellsPotential therapeutic targetRenal inflammationTubulointerstitial injuryRenal functionUUO groupKidney functionProfibrotic mechanismsControl subjectsDisease patients
2020
The Potential Role of Regulatory B Cells in Idiopathic Membranous Nephropathy
Dong Z, Liu Z, Dai H, Liu W, Feng Z, Zhao Q, Gao Y, Liu F, Zhang N, Dong X, Zhou X, Du J, Huang G, Tian X, Liu B. The Potential Role of Regulatory B Cells in Idiopathic Membranous Nephropathy. Journal Of Immunology Research 2020, 2020: 7638365. PMID: 33426094, PMCID: PMC7772048, DOI: 10.1155/2020/7638365.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsIdiopathic membranous nephropathyRegulatory B cellsBreg cellsMembranous nephropathyImmune responseB cellsPathogenesis of IMNDifferent inflammatory environmentsFunction of BregsPathological autoimmune responsesRole of BregsCellular immune responsesHumoral immune responseIMN patientsImmunomodulatory cellsImmunosuppressive roleAutoimmune responseInterleukin-10Autoimmune diseasesImmune cellsInflammatory environmentEarly treatmentT cellsBregsImmunological phenomenaInhibiting calpain 1 and 2 in cyclin G associated kinase–knockout mice mitigates podocyte injury
Tian X, Inoue K, Zhang Y, Wang Y, Sperati CJ, Pedigo CE, Zhao T, Yan M, Groener M, Moledina DG, Ebenezer K, Li W, Zhang Z, Liebermann D, Greene L, Greer P, Parikh CR, Ishibe S. Inhibiting calpain 1 and 2 in cyclin G associated kinase–knockout mice mitigates podocyte injury. JCI Insight 2020, 5: e142740. PMID: 33208557, PMCID: PMC7710277, DOI: 10.1172/jci.insight.142740.Peer-Reviewed Original ResearchConceptsCalpain-1Chronic kidney diseaseDegree of proteinuriaCalpain inhibitor IIIGlomeruli of patientsProgressive proteinuriaCalpain protease activityGlobal glomerulosclerosisGlomerular injuryKidney functionKidney diseaseKidney failureCalcium dysregulationPodocyte injuryPodocyte-specific deletionPodocyte damageG associated kinaseProtective roleCalpain activationProteinuriaGlomerulosclerosisMiceReduced expressionStriking increaseInjuryDynamin 1 is important for microtubule organization and stabilization in glomerular podocytes
La TM, Tachibana H, Li S, Abe T, Seiriki S, Nagaoka H, Takashima E, Takeda T, Ogawa D, Makino S, Asanuma K, Watanabe M, Tian X, Ishibe S, Sakane A, Sasaki T, Wada J, Takei K, Yamada H. Dynamin 1 is important for microtubule organization and stabilization in glomerular podocytes. The FASEB Journal 2020, 34: 16449-16463. PMID: 33070431, DOI: 10.1096/fj.202001240rr.Peer-Reviewed Original ResearchConceptsDynamin 1Microtubule organizationMouse podocytesΑ-tubulinMicrotubule bundlesGlomerular podocytesEndocytic proteinsMicrotubule bundle formationStabilization of microtubulesAcetylated α-tubulinVesicle formationNocodazole resistanceImmunoelectron microscopyMicrotubulesPhysiological significanceBundle formationRat podocytesMurine Epsins Play an Integral Role in Podocyte Function
Wang Y, Pedigo CE, Inoue K, Tian X, Cross E, Ebenezer K, Li W, Wang Z, Shin JW, Schwartze E, Groener M, Ishibe S. Murine Epsins Play an Integral Role in Podocyte Function. Journal Of The American Society Of Nephrology 2020, 31: 2870-2886. PMID: 33051360, PMCID: PMC7790213, DOI: 10.1681/asn.2020050691.Peer-Reviewed Original ResearchConceptsSerum response factorPodocyte-specific lossCell division control protein 42 homologCell adhesionRegulation of Cdc42Integrin expressionProtein Cdc42Membrane proteinsTriple knockout miceEpsinDownstream regulationFoot process effacementPodocyte functionResponse factorPrimary podocytesCdc42Essential roleIndispensable roleProcess effacementExpressionRegulationKnockout miceIntegral rolePodocytesHomologProtective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes
Wang Q, Tian X, Zhou W, Wang Y, Zhao H, Li J, Zhou X, Zhang H, Zhao T, Li P. Protective Role of Tangshen Formula on the Progression of Renal Damage in db/db Mice by TRPC6/Talin1 Pathway in Podocytes. Journal Of Diabetes Research 2020, 2020: 3634974. PMID: 33015191, PMCID: PMC7519445, DOI: 10.1155/2020/3634974.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCell AdhesionCell MovementCell SurvivalCytoskeletonDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 2Disease ProgressionDrugs, Chinese HerbalHumansKidney DiseasesKidney GlomerulusMaleMedicine, Chinese TraditionalMiceMice, Inbred C57BLPodocytesProteinuriaTalinTRPC6 Cation ChannelWound HealingConceptsDiabetic kidney diseasePrimary mouse podocytesTangshen FormulaTransient receptor potential canonical channel 6Renal functionKidney diseaseTSF treatmentMouse podocytesType 2 diabetic kidney diseaseProtective roleDb/db miceAdvanced glycation end productsTRPC6-dependent CaProteinuric kidney diseaseActivated T cells 2Chinese medicine formulaGlycation end productsExpression of Talin1T cells 2Foot process effacementLoss of talin1Renal damageDb micePodocyte numberMurine modelIdentification of Podocyte Cargo Proteins by Proteomic Analysis of Clathrin-Coated Vesicles.
Groener M, Wang Y, Cross E, Tian X, Ebenezer K, Baik E, Pedigo C, Schiffer M, Inoue K, Ishibe S. Identification of Podocyte Cargo Proteins by Proteomic Analysis of Clathrin-Coated Vesicles. Kidney360 2020, 1: 480-490. PMID: 35368594, PMCID: PMC8809311, DOI: 10.34067/kid.0000212020.Peer-Reviewed Original ResearchConceptsClathrin-coated vesiclesCargo proteinsProteomic analysisPodocyte healthPrimary podocyte cultureTransferrin receptor protein 1Endocytic traffickingSignificant proteinsLiquid chromatography-mass spectrometryPodocyte culturesHigh abundanceGenetic ablationSmall vesiclesCCV fractionsProteinProtein 1Protein markersClathrinVesiclesMultiple protein markersDiphtheria toxinFundamental roleMouse kidneyImmunofluorescence stainingCargoRole of Transient Receptor Potential Canonical Channel 6 (TRPC6) in Diabetic Kidney Disease by Regulating Podocyte Actin Cytoskeleton Rearrangement
Wang Q, Tian X, Wang Y, Wang Y, Li J, Zhao T, Li P. Role of Transient Receptor Potential Canonical Channel 6 (TRPC6) in Diabetic Kidney Disease by Regulating Podocyte Actin Cytoskeleton Rearrangement. Journal Of Diabetes Research 2020, 2020: 6897390. PMID: 31998809, PMCID: PMC6964719, DOI: 10.1155/2020/6897390.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDiabetic kidney diseaseTransient receptor potential canonical channel 6Proteinuric kidney diseaseKidney diseaseMechanisms of DKDMultiple pathogenic factorsActin cytoskeleton rearrangementNew therapeutic targetsCytoskeleton rearrangementDKD patientsChannel 6Glomerular injuryPodocyte injuryPathogenic factorsTherapeutic targetDiseaseInjuryPodocytesCritical rolePatientsProgression
2019
Inhibition of Endocytosis of Clathrin-Mediated Angiotensin II Receptor Type 1 in Podocytes Augments Glomerular Injury
Inoue K, Tian X, Velazquez H, Soda K, Wang Z, Pedigo CE, Wang Y, Cross E, Groener M, Shin JW, Li W, Hassan H, Yamamoto K, Mundel P, Ishibe S. Inhibition of Endocytosis of Clathrin-Mediated Angiotensin II Receptor Type 1 in Podocytes Augments Glomerular Injury. Journal Of The American Society Of Nephrology 2019, 30: 2307-2320. PMID: 31511362, PMCID: PMC6900791, DOI: 10.1681/asn.2019010053.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAlbuminuriaAngiotensin IIAnimalsCalcium SignalingCells, CulturedClathrin-Coated VesiclesCreatinineDynamin IDynamin IIEndocytosisGlomerulonephritisHemodynamicsKidney GlomerulusMaleMiceMice, KnockoutNeuropeptidesPodocytesPseudopodiaRac1 GTP-Binding ProteinReceptor, Angiotensin, Type 1ConceptsDouble knockout miceAngiotensin II receptor type 1Receptor type 1Renin-angiotensin system blockersType 1Renin-angiotensin systemPrimary podocytesEffects of AngIIImproved albuminuriaSystem blockersGlomerular hyperfiltrationGlomerular filtration barrierGlomerular injuryKidney functionAngiotensin IIKidney failurePodocyte injuryProtective effectCalcium influxRac1 activationAngII stimulationMice exhibitAngIIGenetic ablationMiceProtective effects of GPR120 agonist-programmed macrophages on renal interstitial fibrosis in unilateral ureteral obstruction (UUO) rats
Wang L, Ren X, Tian XF, Cheng XL, Zhao YY, Li QY, Duan ZY, Tian LF, Chen Z, Lu JM, Liang XY, Zhao YF, Fu RG. Protective effects of GPR120 agonist-programmed macrophages on renal interstitial fibrosis in unilateral ureteral obstruction (UUO) rats. Biomedicine & Pharmacotherapy 2019, 117: 109172. PMID: 31261028, DOI: 10.1016/j.biopha.2019.109172.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBeta CateninBiphenyl CompoundsCytokinesFibrosisGene Expression RegulationKidney DiseasesMacrophages, PeritonealMaleModels, BiologicalPhenotypePhenylpropionatesProtective AgentsRats, Sprague-DawleyReceptors, G-Protein-CoupledSignal TransductionTransforming Growth Factor beta1Ureteral ObstructionVimentinConceptsRenal interstitial fibrosisUnilateral ureteral obstructionInterstitial fibrosisUreteral obstructionProtective effectFree fatty acid receptor GPR120Fatty acid receptor GPR120Unilateral ureteral obstruction operationPeritoneal macrophagesAbnormal expressionExpression of CD206M2 phenotype macrophagesTumor necrosis factorEpithelial-mesenchymal transitionAutologous administrationReceptor GPR120UUO ratsInterleukin-6Intrarenal injectionArginase-1Necrosis factorGPR120 agonistM2 phenotypeΑ-SMATGF-β1Podocyte histone deacetylase activity regulates murine and human glomerular diseases
Inoue K, Gan G, Ciarleglio M, Zhang Y, Tian X, Pedigo CE, Cavanaugh C, Tate J, Wang Y, Cross E, Groener M, Chai N, Wang Z, Justice A, Zhang Z, Parikh CR, Wilson FP, Ishibe S. Podocyte histone deacetylase activity regulates murine and human glomerular diseases. Journal Of Clinical Investigation 2019, 129: 1295-1313. PMID: 30776024, PMCID: PMC6391095, DOI: 10.1172/jci124030.Peer-Reviewed Original ResearchConceptsEarly growth response 1Histone deacetylase 1Proteinuric patientsKidney diseaseHDAC2 activityValproic acidVeterans Aging Cohort StudyEnd-stage kidney diseaseDegree of proteinuriaGlomerular filtration rateAging Cohort StudyInhibition of HDAC1Proteinuric kidney diseaseHuman glomerular diseasesGlomerular disease modelsConnectivity Map databaseCohort studyFiltration rateGlomerular diseaseHistone deacetylase activityProteinuric kidneysHDAC inhibitorsProteinuriaMRNA expressionGenetic ablation
2018
Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling Pathways
Zacchia M, Tian X, Zona E, Alpern RJ, Preisig PA. Acid Stimulation of the Citrate Transporter NaDC-1 Requires Pyk2 and ERK1/2 Signaling Pathways. Journal Of The American Society Of Nephrology 2018, 29: 1720-1730. PMID: 29678998, PMCID: PMC6054333, DOI: 10.1681/asn.2017121268.Peer-Reviewed Original ResearchMeSH KeywordsAcidsAmmonium ChlorideAnimalsCells, CulturedCitric AcidCSK Tyrosine-Protein KinaseDicarboxylic Acid TransportersEndothelin-1Epithelial CellsFocal Adhesion Kinase 2Kidney Tubules, ProximalMAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3OpossumsOrganic Anion Transporters, Sodium-DependentPhosphorylationProto-Oncogene Proteins c-rafReceptor, Endothelin BRibosomal Protein S6 Kinases, 90-kDaSrc-Family KinasesTransfectionConceptsET-1/ETEndothelin-1Proximal tubulesCultured opossum kidney cellsAcid stimulationInhibition of Pyk2ET-1 stimulationRenal proximal tubulesNaDC-1Opossum kidney cellsCl loadingC-SrcPhosphorylation of Raf1Urine citratePyk2 knockdownEnd pointAcid loadApical NaERK1/2 pathwayStimulationMiceKidney cellsKidneyPyk2ERK1/2
2017
Vinculin is required to maintain glomerular barrier integrity
Lausecker F, Tian X, Inoue K, Wang Z, Pedigo CE, Hassan H, Liu C, Zimmer M, Jinno S, Huckle AL, Hamidi H, Ross RS, Zent R, Ballestrem C, Lennon R, Ishibe S. Vinculin is required to maintain glomerular barrier integrity. Kidney International 2017, 93: 643-655. PMID: 29241625, PMCID: PMC5846847, DOI: 10.1016/j.kint.2017.09.021.Peer-Reviewed Original ResearchMeSH KeywordsAlbuminuriaAnimalsCell MovementCell Surface ExtensionsCells, CulturedFocal Adhesion Kinase 1Focal AdhesionsGlomerulonephritis, MembranousGlomerulosclerosis, Focal SegmentalMechanotransduction, CellularMice, Inbred C57BLMice, KnockoutNephrosis, LipoidPhosphorylationPodocytesVinculinZonula Occludens-1 ProteinConceptsIntegrin-mediated cell-matrix adhesionIntercellular junctionsRole of vinculinCell-matrix adhesionFocal adhesion sizeCell-matrix interactionsGlomerular filtration barrierPodocyte-specific knockout miceLocalization of vinculinFiltration barrierCytoplasmic proteinsAdhesion sizeCell protrusionsVinculinActin filamentsPodocyte foot processesCell migrationProtein zonula occludens-1Expression levelsPrimary podocytesMutant miceZonula occludens-1Knockout miceFoot process effacementDramatic differencesLoss 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
2016
Kidney Tubular Ablation of Ocrl/Inpp5b Phenocopies Lowe Syndrome Tubulopathy
Inoue K, Balkin DM, Liu L, Nandez R, Wu Y, Tian X, Wang T, Nussbaum R, De Camilli P, Ishibe S. Kidney Tubular Ablation of Ocrl/Inpp5b Phenocopies Lowe Syndrome Tubulopathy. Journal Of The American Society Of Nephrology 2016, 28: 1399-1407. PMID: 27895154, PMCID: PMC5407733, DOI: 10.1681/asn.2016080913.Peer-Reviewed Original ResearchConceptsEarly embryonic lethalityTransporter 5Dent's diseaseIndependent endocytosisEmbryonic lethalityRedundant functionsType 2 inositolHuman phenotypesProximal tubule endocytosisOculocerebrorenal syndromeGenetic ablationCellular levelGermline knockoutLowe syndromeEndocytosisMouse backgroundMice resultsMutationsInositolLow molecular weight proteinuriaINPP5BParalogsProximal tubule functionDramatic effectOCRL