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
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 increaseInjury
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 ablationMice
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