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 ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCell DeathHumansKidney DiseasesKidney GlomerulusMicePodocytesProfilinsProteinuriaConceptsProteinuric 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 detachmentProteinuriaEffect of pulsed intravenous methylprednisolone with alternative low-dose prednisone on high-risk IgA nephropathy: a 18-month prospective clinical trial
Li Y, Fu R, Gao J, Wang L, Duan Z, Tian L, Ge H, Ma X, Zhang Y, Li K, Xu P, Tian X, Chen Z. Effect of pulsed intravenous methylprednisolone with alternative low-dose prednisone on high-risk IgA nephropathy: a 18-month prospective clinical trial. Scientific Reports 2022, 12: 255. PMID: 34996948, PMCID: PMC8742122, DOI: 10.1038/s41598-021-03691-0.Peer-Reviewed Original ResearchMeSH KeywordsAdministration, IntravenousAdministration, OralAdultDisease ProgressionDrug TaperingDrug Therapy, CombinationFemaleGlomerulonephritis, IGAGlucocorticoidsHumansKidney Failure, ChronicMaleMethylprednisolonePrednisoneProspective StudiesProteinuriaPulse Therapy, DrugRemission InductionRisk AssessmentRisk FactorsTime FactorsTreatment OutcomeConceptsLow-dose prednisoneComplete remissionFP groupIntravenous methylprednisoloneHigh-risk IgA nephropathyOxford MEST-C scoreChinese Clinical Trial RegistryPulsed intravenous methylprednisoloneACEI/ARBClinical Trials RegistryProspective clinical trialsMEST-C scoreFavorable safety profilePercentage of CROral prednisoneTotal remissionAdult patientsNephropathy patientsPrednisone regimenCushing's syndromeMore patientsPrimary outcomeTrials RegistryClinical outcomesIgA nephropathy
2020
Protective 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 model
2019
Podocyte 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
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 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
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