2023
Loss of endothelial glucocorticoid receptor accelerates organ fibrosis in db/db mice
Srivastava S, Goodwin J. Loss of endothelial glucocorticoid receptor accelerates organ fibrosis in db/db mice. American Journal Of Physiology. Renal Physiology 2023, 325: f519-f526. PMID: 37589053, PMCID: PMC10639025, DOI: 10.1152/ajprenal.00105.2023.Peer-Reviewed Original ResearchConceptsEndothelial glucocorticoid receptorGlucocorticoid receptorOrgan fibrosisMouse modelMultiple organsSpontaneous type 2 diabetesDb/db miceDiabetic kidney fibrosisReceptor-mediated upregulationUse of metforminDiabetic renal fibrosisType 2 diabetesMechanisms of fibrosisGenetic mouse modelsUpregulation of WntRenal fibrosisSevere fibrosisDb miceIL-6Key cytokineKidney fibrosisDisease processFibrosisFibrotic conditionsWnt inhibitors
2021
Loss of endothelial glucocorticoid receptor accelerates diabetic nephropathy
Srivastava SP, Zhou H, Setia O, Liu B, Kanasaki K, Koya D, Dardik A, Fernandez-Hernando C, Goodwin J. Loss of endothelial glucocorticoid receptor accelerates diabetic nephropathy. Nature Communications 2021, 12: 2368. PMID: 33888696, PMCID: PMC8062600, DOI: 10.1038/s41467-021-22617-y.Peer-Reviewed Original ResearchMeSH KeywordsAdrenalectomyAnimalsDiabetes Mellitus, ExperimentalDiabetic NephropathiesEndothelial CellsEndotheliumEpithelial-Mesenchymal TransitionFatty AcidsFibrosisGlucocorticoidsHumansHypercholesterolemiaInterleukin-6Kidney TubulesMaleMiceMice, Knockout, ApoEOxidation-ReductionReceptors, GlucocorticoidStreptozocinWnt Signaling PathwayConceptsEndothelial glucocorticoid receptorGlucocorticoid receptorEndothelial cell homeostasisDiabetic miceRenal fibrosisEndothelial cellsMesenchymal transitionSevere renal fibrosisTubular epithelial cellsCell homeostasisFatty acid oxidationDiabetic controlDiabetic nephropathyAntifibrotic moleculesIL-6Kidney fibrosisMesenchymal activationRegulation of diseaseOrgan fibrosisAberrant cytokineFibrogenic phenotypeFibrosisMiceEpithelial cellsDefective regulationEndothelial SIRT3 regulates myofibroblast metabolic shifts in diabetic kidneys
Srivastava SP, Li J, Takagaki Y, Kitada M, Goodwin JE, Kanasaki K, Koya D. Endothelial SIRT3 regulates myofibroblast metabolic shifts in diabetic kidneys. IScience 2021, 24: 102390. PMID: 33981977, PMCID: PMC8086030, DOI: 10.1016/j.isci.2021.102390.Peer-Reviewed Original ResearchDiabetic kidney fibrosisDiabetic kidneyEndothelial cellsKidney fibrosisDefective metabolismRenal tubular epithelial cellsTubular epithelial cellsKidney functionDiabetic miceFibrogenic pathwaysFibrogenic processDisease processLoss of functionMesenchymal transitionKidneyMouse strainsEpithelial cellsGain of functionSIRT3Metabolic reprogrammingMesenchymal transformationFibrosisSIRT3 geneMetabolismCells
2020
Inhibition of Angiotensin-Converting Enzyme Ameliorates Renal Fibrosis by Mitigating DPP-4 Level and Restoring Antifibrotic MicroRNAs
Srivastava SP, Goodwin JE, Kanasaki K, Koya D. Inhibition of Angiotensin-Converting Enzyme Ameliorates Renal Fibrosis by Mitigating DPP-4 Level and Restoring Antifibrotic MicroRNAs. Genes 2020, 11: 211. PMID: 32085655, PMCID: PMC7074526, DOI: 10.3390/genes11020211.Peer-Reviewed Original ResearchMeSH KeywordsAngiotensin Receptor AntagonistsAngiotensin-Converting Enzyme InhibitorsAnimalsCell LineDiabetes Mellitus, ExperimentalDiabetic NephropathiesDipeptidyl Peptidase 4Disease Models, AnimalDrug SynergismGene Expression RegulationHumansMiceMicroRNAsOligopeptidesSignal TransductionTransforming Growth Factor betaConceptsAngiotensin II receptor blockersRenal fibrosisDPP-4End-stage renal diseaseSubstrates of ACEDiabetic kidney diseaseEffect of ACEIII receptor blockersDPP-4 levelsTGFβ signalingAngiotensin converting enzymeChronic nephropathyReceptor blockersRenal diseaseKidney diseaseACEIEnzyme inhibitorsConventional drugsDownregulated expressionEndothelial cellsFibrosisInhibitory effectDrug 1MiR-29AcSDKP
2018
SIRT3 deficiency leads to induction of abnormal glycolysis in diabetic kidney with fibrosis
Srivastava SP, Li J, Kitada M, Fujita H, Yamada Y, Goodwin JE, Kanasaki K, Koya D. SIRT3 deficiency leads to induction of abnormal glycolysis in diabetic kidney with fibrosis. Cell Death & Disease 2018, 9: 997. PMID: 30250024, PMCID: PMC6155322, DOI: 10.1038/s41419-018-1057-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarnitine O-PalmitoyltransferaseCell LineDiabetes Mellitus, ExperimentalDiabetic NephropathiesFibrosisGene Knockdown TechniquesGlucoseGlycolysisHumansHypoxia-Inducible Factor 1, alpha SubunitKidneyMiceMice, Inbred C57BLPeroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alphaPyruvate KinaseSirtuin 3StreptozocinTransfectionTransforming Growth Factor beta2ConceptsDiabetic kidneyAbnormal glycolysisAberrant glycolysisSIRT3 suppressionMouse modelProgressive diabetic kidney diseaseDiabetic kidney diseaseDiabetic mouse modelAberrant glucose metabolismSIRT3 protein levelsSIRT3 siRNADiabetic miceKidney diseaseKidney fibrosisSystemic administrationFibrogenic pathwaysSIRT3 deficiencyGlucose metabolismTherapeutic targetFibrosisSIRT3 levelsHIF1α accumulationFibrogenic phenotypeKidneyGrowth factor