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
Podocyte Glucocorticoid Receptors Are Essential for Glomerular Endothelial Cell Homeostasis in Diabetes Mellitus
Srivastava SP, Zhou H, Setia O, Dardik A, Fernandez‐Hernando C, Goodwin J. Podocyte Glucocorticoid Receptors Are Essential for Glomerular Endothelial Cell Homeostasis in Diabetes Mellitus. Journal Of The American Heart Association 2021, 10: e019437. PMID: 34308664, PMCID: PMC8475689, DOI: 10.1161/jaha.120.019437.Peer-Reviewed Original ResearchConceptsDiabetic nephropathySegmental fibrosisFatty acid metabolismDiabetes mellitusEndothelial cellsPrimary podocytesReceptor knockout micePathogenesis of proteinuriaAdministration of streptozotocinProfibrotic gene expressionAcid metabolismGlomerular endothelial cellsSmooth muscle actinEndothelial cell homeostasisCarnitine palmitoyltransferase 1AFatty acid oxidationBackground ProteinuriaWorsened fibrosisClinical characteristicsFibrotic featuresGlomerular fibrosisGlomerular homeostasisPatient managementControl littermatesSevere diseaseLoss 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 regulationLoss of endothelial glucocorticoid receptor promotes angiogenesis via upregulation of Wnt/β-catenin pathway
Liu B, Zhou H, Zhang T, Gao X, Tao B, Xing H, Zhuang Z, Dardik A, Kyriakides TR, Goodwin JE. Loss of endothelial glucocorticoid receptor promotes angiogenesis via upregulation of Wnt/β-catenin pathway. Angiogenesis 2021, 24: 631-645. PMID: 33650028, PMCID: PMC8292305, DOI: 10.1007/s10456-021-09773-x.Peer-Reviewed Original ResearchConceptsWnt/β-catenin signalingWnt/β-catenin pathwayΒ-catenin signalingΒ-catenin pathwayAutophagy fluxKey biological processesGlucocorticoid receptorNuclear receptor familyTube formation assaysEndothelial cellsBiological processesCanonical WntP62 degradationReceptor familyFormation assaysAbsence of GRCell viability assaysProcess of angiogenesisWntGR regulationSignalingVivo assaysQuantitative PCRKey receptorPathway
2020
Metabolic reprogramming by N‐acetyl‐seryl‐aspartyl‐lysyl‐proline protects against diabetic kidney disease
Srivastava SP, Goodwin JE, Kanasaki K, Koya D. Metabolic reprogramming by N‐acetyl‐seryl‐aspartyl‐lysyl‐proline protects against diabetic kidney disease. British Journal Of Pharmacology 2020, 177: 3691-3711. PMID: 32352559, PMCID: PMC7393199, DOI: 10.1111/bph.15087.Peer-Reviewed Original ResearchConceptsACE inhibitorsDiabetic kidneyKidney fibrosisEffects of ACEIsEnd-stage renal diseaseDiabetic CD-1 miceKidney cell metabolismAbnormal glucose metabolismDiabetic kidney diseaseFirst-line drugsCD-1 miceMesenchymal transformationFatty acid oxidationMitochondrial fatty acid oxidationAntifibrotic mediatorsFatty acid metabolismDiabetic patientsRenal diseaseAntifibrotic mechanismsSevere fibrosisACE inhibitionKidney diseaseAntifibrotic actionReceptor antagonistC57BL6 miceInhibition 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-29AcSDKPEndothelial cell–glucocorticoid receptor interactions and regulation of Wnt signaling
Zhou H, Mehta S, Srivastava SP, Grabinska K, Zhang X, Wong C, Hedayat A, Perrotta P, Fernández-Hernando C, Sessa WC, Goodwin JE. Endothelial cell–glucocorticoid receptor interactions and regulation of Wnt signaling. JCI Insight 2020, 5: e131384. PMID: 32051336, PMCID: PMC7098785, DOI: 10.1172/jci.insight.131384.Peer-Reviewed Original ResearchConceptsEndothelial glucocorticoid receptorVascular inflammationGlucocorticoid receptorGlucocorticoid receptor regulationGlucocorticoid receptor resultsUpregulation of WntEndogenous glucocorticoidsExogenous glucocorticoidsGlucocorticoid response elementCardiovascular diseaseMouse endothelial cellsMouse modelEndothelial WNTInflammationReceptor regulationEndothelial cellsReceptors resultsNext-generation sequencingReceptor interactionReceptorsRegulation of WntWnt pathwayGlucocorticoidsRecent dataWnt
2019
The Glucocorticoid Receptor in Cardiovascular Health and Disease
Liu B, Zhang TN, Knight JK, Goodwin JE. The Glucocorticoid Receptor in Cardiovascular Health and Disease. Cells 2019, 8: 1227. PMID: 31601045, PMCID: PMC6829609, DOI: 10.3390/cells8101227.Peer-Reviewed Original ResearchConceptsGlucocorticoid receptorGlucocorticoid signalingCardiovascular systemNon-genomic pathwaysClinical outcomesExogenous glucocorticoidsGlucocorticoid treatmentCardiovascular healthCardiovascular diseaseNuclear receptor familyTherapeutic strategiesAnimal modelsSteroid hormone cortisolHormone cortisolPathological conditionsReceptorsDiseaseReceptor familySignalingDistinct gene networksHuman diseasesDirect effectCritical roleInflammationPrognosisCharacterization of Circular RNA and microRNA Profiles in Septic Myocardial Depression: a Lipopolysaccharide-Induced Rat Septic Shock Model
Zhang TN, Yang N, Goodwin JE, Mahrer K, Li D, Xia J, Wen R, Zhou H, Zhang T, Song WL, Liu CF. Characterization of Circular RNA and microRNA Profiles in Septic Myocardial Depression: a Lipopolysaccharide-Induced Rat Septic Shock Model. Inflammation 2019, 42: 1990-2002. PMID: 31332662, DOI: 10.1007/s10753-019-01060-8.Peer-Reviewed Original ResearchConceptsCircular RNAsDifferential expressionGene Ontology term enrichmentFeatures of circRNAsMiRNA-mRNA networkMicroRNA profilesBasic molecular mechanismsNovel miRNAsCellular functionsRegulatory networksTerm enrichmentRNA sequencingBioinformatics analysisComprehensive circRNARegulator networkRegulatory relationshipsMolecular mechanismsCircRNAsMetabolic processesMiRNAsHeart tissueBiological mechanismsMiRNARNAPathological processesRole of the glucocorticoid receptor in glomerular disease
Goodwin JE. Role of the glucocorticoid receptor in glomerular disease. American Journal Of Physiology. Renal Physiology 2019, 317: f133-f136. PMID: 31166704, PMCID: PMC6692724, DOI: 10.1152/ajprenal.00217.2019.Peer-Reviewed Original ResearchConceptsGlomerular diseasePotent anti-inflammatory agentSteroid delivery systemsAnti-inflammatory agentsSystemic steroidsBeneficial direct effectsUnfavorable riskSystemic administrationTherapeutic benefitGlucocorticoid receptorRisk assessment algorithmClinicians' effortsBenefit ratioVivo studiesGlucocorticoidsDiseasePersonalized medicineDirect effectDelivery systemGlomeruliSteroidsAdministrationPodocytesReceptors
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
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
2015
Endothelial Glucocorticoid Receptor Suppresses Atherogenesis—Brief Report
Goodwin JE, Zhang X, Rotllan N, Feng Y, Zhou H, Fernández-Hernando C, Yu J, Sessa WC. Endothelial Glucocorticoid Receptor Suppresses Atherogenesis—Brief Report. Arteriosclerosis Thrombosis And Vascular Biology 2015, 35: 779-782. PMID: 25810297, PMCID: PMC4375730, DOI: 10.1161/atvbaha.114.304525.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic DiseasesApolipoproteins EAtherosclerosisBody WeightBrachiocephalic TrunkCholesterolDiet, High-FatDisease Models, AnimalEndothelial CellsGenotypeMacrophagesMice, Inbred C57BLMice, KnockoutPhenotypeReceptors, GlucocorticoidSeverity of Illness IndexTime FactorsTriglyceridesConceptsEndothelial glucocorticoid receptorGlucocorticoid receptorHigh-fat diet feedingApoE knockout backgroundSevere atherosclerotic lesionsGroups of micePathogenesis of atherosclerosisAortic sinusTotal cholesterolAtherosclerosis progressionBrachiocephalic arteryControl miceInflammatory milieuTonic inhibitionDiet feedingMacrophage recruitmentAtherosclerotic lesionsBody weightMiceKnockout backgroundReceptorsLesionsAtherosclerosisInflammationArtery
2014
Loss of the Endothelial Glucocorticoid Receptor Prevents the Therapeutic Protection Afforded by Dexamethasone after LPS
Goodwin JE, Feng Y, Velazquez H, Zhou H, Sessa WC. Loss of the Endothelial Glucocorticoid Receptor Prevents the Therapeutic Protection Afforded by Dexamethasone after LPS. PLOS ONE 2014, 9: e108126. PMID: 25299055, PMCID: PMC4191990, DOI: 10.1371/journal.pone.0108126.Peer-Reviewed Original ResearchConceptsKO miceLow-dose LPSSepsis-like syndromeAnti-inflammatory therapyInflammatory cytokines TNFKO mice showRegulation of NFNF-κB activationNitric oxide releaseTherapeutic protectionIL-6INOS productionCytokines TNFReceptor preventsIdentical doseControl animalsMice showGlucocorticoid receptorOxide releaseDexamethasoneLPSMiceProlonged activationActivationSepsis
2012
Endothelial glucocorticoid receptor is required for protection against sepsis
Goodwin JE, Feng Y, Velazquez H, Sessa WC. Endothelial glucocorticoid receptor is required for protection against sepsis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 110: 306-311. PMID: 23248291, PMCID: PMC3538225, DOI: 10.1073/pnas.1210200110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisCorticosteroneEndotheliumGene DeletionHemodynamicsHuman Umbilical Vein Endothelial CellsHumansIn Situ Nick-End LabelingInterleukin-6LipopolysaccharidesMaleMiceMice, KnockoutNF-kappa BNitric OxideNitric Oxide Synthase Type IINitric Oxide Synthase Type IIIReceptors, GlucocorticoidSepsisTumor Necrosis Factor-alphaConceptsEndothelial nitric oxide synthaseEndothelial glucocorticoid receptorHuman umbilical vein cellsGlucocorticoid receptorInterleukin-6Inducible nitric oxide synthase (iNOS) expressionExpression of eNOSNitric oxide synthase expressionHigher nitric oxide levelsOxide synthase expressionNitric oxide levelsNF-κB levelsSpecific iNOS inhibitorNitric oxide synthaseNitric oxide synthesisNF-κB activationRate of apoptosisHemodynamic collapseHemodynamic instabilityTissue-specific deletionUmbilical vein cellsInflammatory cytokinesINOS inhibitorTumor necrosisOxide synthase
2011
Glucocorticoid-induced hypertension
Goodwin JE, Geller DS. Glucocorticoid-induced hypertension. Pediatric Nephrology 2011, 27: 1059-1066. PMID: 21744056, DOI: 10.1007/s00467-011-1928-4.BooksConceptsGlucocorticoid-induced hypertensionForms of hypertensionGlucocorticoid receptorRenal mineralocorticoid receptorsCommon clinical problemVascular smooth muscleBlood pressure regulationVascular endothelial cellsTissue-specific contributionsMineralocorticoid receptorTreatment strategiesClinical dataHypertensionSmooth muscleClinical problemAnimal modelsKidney tissuePressure regulationOrgan systemsWater reabsorptionEndothelial cellsExtra-vascular tissuesReceptorsPathogenesisMouse geneticsKnockout of the vascular endothelial glucocorticoid receptor abrogates dexamethasone-induced hypertension
Goodwin JE, Zhang J, Gonzalez D, Albinsson S, Geller DS. Knockout of the vascular endothelial glucocorticoid receptor abrogates dexamethasone-induced hypertension. Journal Of Hypertension 2011, 29: 1347-1356. PMID: 21659825, PMCID: PMC3439131, DOI: 10.1097/hjh.0b013e328347da54.Peer-Reviewed Original ResearchConceptsEndothelial glucocorticoid receptorGlucocorticoid receptorMean blood pressure increaseKnockout animalsDexamethasone-induced hypertensionBlood pressure increaseCircadian BP rhythmForms of hypertensionEffects of glucocorticoidsNormal circadian BP rhythmPeripheral circadian clocksBaseline BPBP rhythmMmHg increaseContractile responseBP homeostasisResistance arteriolesTissue-specific knockoutFundamental physiologic processesDexamethasone treatmentHypertensionMouse modelControl animalsVascular endotheliumKnockout mice
2010
The glucocorticoid receptor in the distal nephron is not necessary for the development or maintenance of dexamethasone-induced hypertension
Goodwin JE, Zhang J, Velazquez H, Geller DS. The glucocorticoid receptor in the distal nephron is not necessary for the development or maintenance of dexamethasone-induced hypertension. Biochemical And Biophysical Research Communications 2010, 394: 266-271. PMID: 20188070, PMCID: PMC2946623, DOI: 10.1016/j.bbrc.2010.02.123.Peer-Reviewed Original ResearchConceptsGlucocorticoid-induced hypertensionGlucocorticoid receptorDistal nephronKnockout miceSimilar hypertensive responsesBaseline blood pressureDevelopment of hypertensionReceptor knockout miceAdministration of glucocorticoidsSimilar body weightGlucocorticoid receptor actionHypertensive responseRenal histologyBlood pressureUrinary excretionTissue-specific knockoutMineralocorticoid receptorHypertensionMouse modelLittermate controlsNephron numberSide effectsBody weightReceptor actionImportant mediator
2008
Characterization of a Novel Gain of Function Glucocorticoid Receptor Knock-in Mouse*
Zhang J, Ge R, Matte-Martone C, Goodwin J, Shlomchik WD, Mamula MJ, Kooshkabadi A, Hardy MP, Geller D. Characterization of a Novel Gain of Function Glucocorticoid Receptor Knock-in Mouse*. Journal Of Biological Chemistry 2008, 284: 6249-6259. PMID: 19017639, PMCID: PMC2649105, DOI: 10.1074/jbc.m807997200.Peer-Reviewed Original ResearchConceptsHuman glucocorticoid receptorStudies of glucocorticoidsAdrenocortical sizeGR altersEndogenous glucocorticoidsACTH levelsAdrenal axisReceptor knockImmunologic studiesWild-type GRMaintenance of homeostasisCorticosterone levelsGlucocorticoid receptorGlucocorticoidsNovel gainPhysiologic functionMicePathological processesMutant GRGC functionBasal regulationVivoGC physiologyHomologous recombinationHuman diseasesA Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension
Goodwin JE, Zhang J, Geller DS. A Critical Role for Vascular Smooth Muscle in Acute Glucocorticoid-Induced Hypertension. Journal Of The American Society Of Nephrology 2008, 19: 1291-1299. PMID: 18434569, PMCID: PMC2440298, DOI: 10.1681/asn.2007080911.Peer-Reviewed Original ResearchConceptsVascular smooth muscleAcute hypertensive responseHypertensive responseKO miceSmooth muscleGC receptorChronic hypertensive responseGlucocorticoid-Induced HypertensionNormal circadian variationBaseline BPTissue-specific knockoutMineralocorticoid receptorMouse modelHypertensionExcess reabsorptionCircadian variationCritical roleMiceReceptorsPromiscuous activationMuscleVivoKnockoutResponseGlucocorticoids