2024
Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy
Jiang H, Shen Z, Zhuang J, Lu C, Qu Y, Xu C, Yang S, Tian X. Understanding the podocyte immune responses in proteinuric kidney diseases: from pathogenesis to therapy. Frontiers In Immunology 2024, 14: 1335936. PMID: 38288116, PMCID: PMC10822972, DOI: 10.3389/fimmu.2023.1335936.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsMeSH KeywordsEndothelial CellsGlomerular Basement MembraneHumansImmunityPodocytesRenal Insufficiency, ChronicConceptsChronic kidney diseaseGlomerular filtration barrierProteinuric glomerular diseasesKidney diseaseGlomerular diseaseImmune responseFiltration barrierTherapeutic targetCell-like characteristicsFocal segmental glomerulosclerosisProteinuric kidney diseaseTargets of immune responsesDamage to podocytesLupus nephritisPotential therapeutic targetGlomerular basement membraneImmune injuryGlomerular injuryMembranous nephropathyFenestrated endothelial cellsKidney functionSegmental glomerulosclerosisAdaptive immunityEpithelial cellsPathogenic mechanisms
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 detachmentProteinuria
2021
AMP-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 Adult
2020
Inhibiting 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 modelIdiopathic Membranous Nephropathy: Glomerular Pathological Pattern Caused by Extrarenal Immunity Activity
Liu W, Gao C, Liu Z, Dai H, Feng Z, Dong Z, Zheng Y, Gao Y, Tian X, Liu B. Idiopathic Membranous Nephropathy: Glomerular Pathological Pattern Caused by Extrarenal Immunity Activity. Frontiers In Immunology 2020, 11: 1846. PMID: 33042109, PMCID: PMC7524879, DOI: 10.3389/fimmu.2020.01846.BooksMeSH KeywordsAutoantibodiesAutoantigensGlomerulonephritis, MembranousHumansModels, ImmunologicalPodocytesConceptsIdiopathic membranous nephropathyGlomerular lesionsThrombospondin type-1 domain-containing 7APathological patternsImmune complex depositionDevelopment of proteinuriaM-type receptorNeural epidermal growthSecretory phospholipase A2Glomerular basement membraneIgG4 predominanceProteinuria remissionCirculating AntibodiesClinical featuresGlomerular damageMembranous nephropathySpontaneous remissionAutoimmune responseComplex depositionExtrarenal tissuesImmune activityAutoimmunity initiationClinical practicePathogenesis modelTHSD7A antigenIdentification 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 ablationMicePodocyte 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
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
Targeting the podocyte cytoskeleton: from pathogenesis to therapy in proteinuric kidney disease
Tian X, Ishibe S. Targeting the podocyte cytoskeleton: from pathogenesis to therapy in proteinuric kidney disease. Nephrology Dialysis Transplantation 2016, 31: 1577-1583. PMID: 26968197, PMCID: PMC5039341, DOI: 10.1093/ndt/gfw021.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsProteinuric kidney diseaseKidney diseaseGlomerular filtration barrierChronic kidney diseaseLack of therapyFiltration barrierIntact glomerular filtration barrierMillions of patientsImportance of podocytesHuman nephrotic syndromeGlomerular injuryNephrotic syndromeTherapeutic implicationsTherapeutic targetPodocyte actin cytoskeletonDisease pathogenesisExciting new dataPathogenesisEpithelial cellsGenetic mutationsDiseasePodocyte cytoskeletonTherapyProgressionPodocytes
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
Podocyte-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
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 synapsesSynaptojaninEndophilin