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
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