2025
PET imaging evidence of HDAC6 suppression in the amygdala across species in PTSD
Bonomi R, Naganawa M, McRiley D, Toyonaga T, LeVasseur B, Duman C, Huang Y, Matuskey D, Carson R, Pietrzak R, Girgenti M, Cosgrove K. PET imaging evidence of HDAC6 suppression in the amygdala across species in PTSD. Molecular Psychiatry 2025, 1-8. PMID: 40753309, DOI: 10.1038/s41380-025-03124-8.Peer-Reviewed Original ResearchPosttraumatic stress disorderPathophysiology of posttraumatic stress disorderNon-trauma-exposed controlsAmygdala of individualsProlonged stress modelBrain imaging studiesStress disorderRodent findingsNuclear translocation of glucocorticoid receptorTranslocation of glucocorticoid receptorHuman findingsTranslational findingsCortisol signalingAmygdalaGlucocorticoid receptorComplex disorderImaging studiesDisordersLongitudinal analysisStress modelHistone deacetylase 6Pharmacological targetsHistone deacetylasesFindingsNuclear translocationIncreased HSD11β1 Expression in Human Leiomyomatous Uteri: Implication for Enhanced Glucocorticoid Signaling
Malcom C, Guzeloglu-Kayisli O, Un B, New E, Cetinkaya-Un B, Guo X, Mikhail E, Imudia A, Lockwood C, Kayisli U. Increased HSD11β1 Expression in Human Leiomyomatous Uteri: Implication for Enhanced Glucocorticoid Signaling. The Journal Of Clinical Endocrinology & Metabolism 2025, dgaf255. PMID: 40290045, DOI: 10.1210/clinem/dgaf255.Peer-Reviewed Original ResearchHuman endometrial stromal cellsUterine leiomyomaFKBP51 levelsHuman endometrial stromal cell culturesLeiomyoma pathogenesisGlucocorticoid receptorSmooth muscle genesTreated with vehicleBinds glucocorticoid receptorEndometrial stromal cellsHydroxysteroid 11-beta dehydrogenase 1HSD11B1 mRNALeiomyomatous uteriGR-mediated transcriptionLeiomyoma cellsNormal myometriumLeiomyoma tissueLeiomyomaMyometriumGR signalingDEX-treatedGlucocorticoid signalingLeiomyoma culturesStromal cellsMuscle genesLupus and inflammatory bowel disease share a common set of microbiome features distinct from other autoimmune disorders
Zhou H, Balint D, Shi Q, Vartanian T, Kriegel M, Brito I. Lupus and inflammatory bowel disease share a common set of microbiome features distinct from other autoimmune disorders. Annals Of The Rheumatic Diseases 2025, 84: 93-105. PMID: 39874239, PMCID: PMC11868722, DOI: 10.1136/ard-2024-225829.Peer-Reviewed Original ResearchProtein-protein interaction analysisMicrobial signaturesMicrobial profilesEffector-like proteinsSignaling pathwayInterleukin-12 signaling pathwayDisease mechanismsBacteria-derived proteinsMetagenomic datasetsMicrobiome featuresMicrobial underpinningsFunctional genesMicrobial biomarkersInteraction analysisMicrobial influenceInflammatory bowel diseaseMicrobial mechanismsGlucocorticoid signalingProteinGlucocorticoid receptorCritical roleAutoimmune diseasesPathwayBowel diseasePotential importance
2024
6421 Imaging Phenotype May Predict Genotype In Human Pheochromocytoma: Relationships Between Genetic Mutation Clusters, Metabolite Transporter Expression, And Radiotracer Uptake
Sakuma I, Fujimoto M, Vatner D, Yokote K, Tanaka T. 6421 Imaging Phenotype May Predict Genotype In Human Pheochromocytoma: Relationships Between Genetic Mutation Clusters, Metabolite Transporter Expression, And Radiotracer Uptake. Journal Of The Endocrine Society 2024, 8: bvae163.210. PMCID: PMC11455308, DOI: 10.1210/jendso/bvae163.210.Peer-Reviewed Original ResearchGATA binding protein 3Expression of norepinephrine transporterGlucose transporter 1Chromaffin cell differentiationNorepinephrine transporter expressionNorepinephrine transporterFDG-PETGlucocorticoid receptorCluster 1 mutationsRadiotracer uptakeLevels of norepinephrine transportersGlucose transporter 1 expressionLocalization of pheochromocytomaChromaffin cell phenotypeCluster 2 tumorsExpression of glucose transporter 1Binding protein-3Expression levelsTumor gene expressionNorepinephrine transporter geneLevels of glucose transporter 1Cell differentiationTranscription factor Phox2aPositron emission tomographyFDG avidity
2023
YIV-818-A: a novel therapeutic agent in prostate cancer management through androgen receptor downregulation, glucocorticoid receptor inhibition, epigenetic regulation, and enhancement of apalutamide, darolutamide, and enzalutamide efficacy
Lam W, Arammash M, Cai W, Guan F, Jiang Z, Liu S, Cheng P, Cheng Y. YIV-818-A: a novel therapeutic agent in prostate cancer management through androgen receptor downregulation, glucocorticoid receptor inhibition, epigenetic regulation, and enhancement of apalutamide, darolutamide, and enzalutamide efficacy. Frontiers In Pharmacology 2023, 14: 1244655. PMID: 37860121, PMCID: PMC10582333, DOI: 10.3389/fphar.2023.1244655.Peer-Reviewed Original ResearchCastration-resistant prostate cancerAR target genesActive compoundsAnti-prostate cancer drugProstate cancerSynergistic effectGlucocorticoid receptorPotential drug candidatesDrug discovery platformRA-VIILuciferase activityKey active compoundsGlucocorticoid receptor inhibitionProstate cancer managementNovel therapeutic agentsRA-VDrug candidatesCompoundsDeprivation therapySafety profileCancer deathExtra-terminal (BET) proteinsGR activityReceptor inhibitionAR inhibitionEndothelial Dysfunction in Cardiorenal Conditions: Implications of Endothelial Glucocorticoid Receptor-Wnt Signaling
Akhter M, Goodwin J. Endothelial Dysfunction in Cardiorenal Conditions: Implications of Endothelial Glucocorticoid Receptor-Wnt Signaling. International Journal Of Molecular Sciences 2023, 24: 14261. PMID: 37762564, PMCID: PMC10531724, DOI: 10.3390/ijms241814261.Peer-Reviewed Original ResearchConceptsGlucocorticoid receptorEndothelial dysfunctionVascular inflammationEndothelial cellsEndothelial glucocorticoid receptorAnti-inflammatory effectsFatty acid oxidation pathwayDifferent pathological conditionsSuppression of WntRenal diseaseInflammatory cascadeVascular toneNovel therapiesMultiple organsBlood fluidityEndothelial integrityPlatelet aggregationInnermost liningVessel permeabilityBlood vesselsPathological conditionsWnt pathwayInflammationDysfunctionDevastating diseaseLoss 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 inhibitorsAbstract 667: Endothelial Glucocorticoid Receptor Deficiency Affects Arteriovenous Fistula Maturation
Zhang W, Gonzalez L, Thaxton C, Ohashi Y, aoyagi Y, Xie Y, Cai Y, Shu C, Goodwin J, Dardik A. Abstract 667: Endothelial Glucocorticoid Receptor Deficiency Affects Arteriovenous Fistula Maturation. Arteriosclerosis Thrombosis And Vascular Biology 2023, 43 DOI: 10.1161/atvb.43.suppl_1.667.Peer-Reviewed Original ResearchEndothelial glucocorticoid receptorChronic kidney diseaseArteriovenous fistulaFl/flControl miceNeointimal hyperplasiaGlucocorticoid receptorAVF diameterVascular inflammationVenous remodelingEnd-stage chronic kidney diseaseAggressive neointimal hyperplasiaPostoperative day 7Arteriovenous fistula maturationPostoperative day 21AVF maturationFistula maturationAortic diameterHemodialysis accessKidney diseaseReceptor deficiencyP-Smad2Body weightDay 21Day 3
2021
TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states
Xu S, Liu Y, Hu R, Wang M, Stöhr O, Xiong Y, Chen L, Kang H, Zheng L, Cai S, He L, Wang C, Copps K, White M, Miao J. TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiological states. ELife 2021, 10: e57462. PMID: 34622775, PMCID: PMC8555985, DOI: 10.7554/elife.57462.Peer-Reviewed Original ResearchConceptsGluconeogenic gene promotersBinding of GRGene promoterGlucocorticoid receptorGlucose homeostasisLigand-binding domainGlucose productionOverexpression of TAZHepatic glucose homeostasisWW domainsBlood glucose concentrationPhysiological fastingGluconeogenic genesGR response elementResponse elementNovel roleTAZNormal physiological stateGR transactivationPhysiological statePromoterMouse liverPericentral hepatocytesPathological statesGlucose concentrationICBP90 Regulates MIF Expression, Glucocorticoid Sensitivity, and Apoptosis at the MIF Immune Susceptibility Locus
Yao J, Leng L, Fu W, Li J, Bronner C, Bucala R. ICBP90 Regulates MIF Expression, Glucocorticoid Sensitivity, and Apoptosis at the MIF Immune Susceptibility Locus. Arthritis & Rheumatology 2021, 73: 1931-1942. PMID: 33844457, DOI: 10.1002/art.41753.Peer-Reviewed Original ResearchMeSH KeywordsAllelesApoptosisCCAAT-Enhancer-Binding ProteinsCell LineFibroblastsGene Expression RegulationGenetic LociGenetic Predisposition to DiseaseGenotypeGlucocorticoidsHumansIntramolecular OxidoreductasesMacrophage Migration-Inhibitory FactorsPromoter Regions, GeneticReceptors, GlucocorticoidUbiquitin-Protein LigasesConceptsMacrophage migration inhibitory factorAutoimmune disease severityMIF -794 CATTRheumatoid synovial fibroblastsMIF expressionGlucocorticoid receptorGlucocorticoid sensitivitySynovial fibroblastsT cellsDisease severityPeripheral blood T cellsBlood T cellsMigration inhibitory factorGlucocorticoid-treated cellsAP-1Glucocorticoid immunosuppressionMIF promoterMIF genotypeMIF polymorphismsFactor antibodyInflammatory responseT lymphocytesActivator protein-1Glucocorticoid responsivenessInhibitory factorLoss 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 receptorPathwayChapter 9 Mechanism of glucocorticoid action in immunology—Basic concepts
Wood M, Whirledge S. Chapter 9 Mechanism of glucocorticoid action in immunology—Basic concepts. 2021, 147-170. DOI: 10.1016/b978-0-12-818508-7.00020-8.Peer-Reviewed Original ResearchGlucocorticoid receptorEpigenetic modificationsPosttranslational modificationsTranscription factorsDNA bindingTissue-specific immune responsesOverall physiologyCell typesGlucocorticoid-mediated effectsNuclear receptorsImmune cell typesFundamental processesReceptor isoformsLevels of hormonesRelative expressionReceptor actionReproductive systemChapter 9 MechanismsGlucocorticoid bioavailabilityAutoimmune diseasesGlucocorticoid actionImmune responseFetal developmentCo-factorImmune system
2020
A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks
Karin O, Raz M, Tendler A, Bar A, Korem Kohanim Y, Milo T, Alon U. A new model for the HPA axis explains dysregulation of stress hormones on the timescale of weeks. Molecular Systems Biology 2020, 16: msb209510. PMID: 32672906, PMCID: PMC7364861, DOI: 10.15252/msb.20209510.Peer-Reviewed Original ResearchConceptsHPA axisPathophysiology of stress-related disordersHypothalamic-pituitary-adrenal (HPA) axisStress-related disordersImpaired glucocorticoid receptorDysregulation of cortisolGlucocorticoid receptorHPA hormonesMood disordersPsychiatric disordersChronic stressStress hormonesMass changesDisordersACTH dynamicsComplex network of hormonesTimescales of weeksDysregulationGland massGrowth factorNetwork of hormonesHormoneGlandCancer Biology and Prevention in Diabetes
Srivastava SP, Goodwin JE. Cancer Biology and Prevention in Diabetes. Cells 2020, 9: 1380. PMID: 32498358, PMCID: PMC7349292, DOI: 10.3390/cells9061380.Peer-Reviewed Original ResearchConceptsDPP-4 inhibitorsMesenchymal transitionType II diabetes mellitusCancer biologySite-specific cancersDevelopment of hyperglycemiaAnti-diabetic therapyRisk of cancerDipeptidyl peptidase-4New therapeutic approachesPossible mechanistic linkMolecular pathological mechanismsDiabetes mellitusSGLT2 inhibitorsChronic inflammationCancer-causing mechanismsDiabetic conditionsTumor cell extravasationAntidiabetic drugsTherapeutic approachesEpidemiological dataPeptidase-4DiabetesPathological mechanismsGlucocorticoid receptortrans-Resveratrol ameliorates anxiety-like behaviors and neuropathic pain in mouse model of post-traumatic stress disorder
Yuan Y, Zhen L, Li Z, Xu W, Leng H, Xu W, Zheng V, Luria V, Pan J, Tao Y, Zhang H, Cao S, Xu Y. trans-Resveratrol ameliorates anxiety-like behaviors and neuropathic pain in mouse model of post-traumatic stress disorder. Journal Of Psychopharmacology 2020, 34: 726-736. PMID: 32308103, DOI: 10.1177/0269881120914221.Peer-Reviewed Original ResearchConceptsBrain-derived neurotrophic factor (BDNF) expressionPhosphorylated cAMP response elementAnxiety-like behaviorNeurotrophic factor expressionNeuropathic painCAMP response elementBrain-derived neurotrophic factor levelsGlucocorticoid receptorFactor expressionProlonged stressStress-induced anxiety-like behaviorStress disorderCold allodynia testsNeurotrophic factor levelsAdrenal axis functionPain-related regionsLocomotor activity testSerum corticosterone levelsMarble burying testNumber of marblesProtein kinase APost-traumatic stress disorderEnzyme-linked immunosorbentClassical animal modelsResponse elementImpact of Monosodium Glutamate and Corticosterone in the Hippocampus: Glucocorticoid Regulation and Caspase‐3 mediated Microvascular and Neuronal Apoptosis
Mathew S, Joy K. Impact of Monosodium Glutamate and Corticosterone in the Hippocampus: Glucocorticoid Regulation and Caspase‐3 mediated Microvascular and Neuronal Apoptosis. The FASEB Journal 2020, 34: 1-1. DOI: 10.1096/fasebj.2020.34.s1.02786.Peer-Reviewed Original ResearchBlood-brain barrierExposure to monosodium glutamateGlucocorticoid receptorApoptotic signaling cascadeEnhanced glucocorticoid receptorDay 8Immediate response to stressEffects of corticosteroneResponse to stressCaspase-3Corticosterone exposureCorticosterone modelBody weightGlutamate modelGroup I control ratsMonosodium glutamate modelDentate gyrusBax-dependent apoptotic pathwayMonosodium glutamateHippocampusNeuronal apoptosisSignaling cascadesGene expressionGroup II ratsMale Wistar ratsA Novel Radioligand Reveals Tissue Specific Pharmacological Modulation of Glucocorticoid Receptor Expression with Positron Emission Tomography
Huang Y, Zhao N, Wang Y, Truillet C, Wei J, Blecha J, VanBrocklin H, Seo Y, Sayeed M, Feldman B, Aggarwal R, Behr S, Shao H, Wilson D, Villanueva-Meyer J, Gestwicki J, Evans M. A Novel Radioligand Reveals Tissue Specific Pharmacological Modulation of Glucocorticoid Receptor Expression with Positron Emission Tomography. ACS Chemical Biology 2020, 15: 1381-1391. PMID: 32255605, PMCID: PMC8031368, DOI: 10.1021/acschembio.9b01043.Peer-Reviewed Original ResearchConceptsPositron emission tomographyBind GRGlucocorticoid receptorEmission tomographyGR agonist dexamethasoneGlucocorticoid receptor expressionGR modulatorsAdipose tissue of miceGR expression levelsTissues of miceReceptor expressionAgonist dexamethasoneArylboronic acid pinacol estersGR expressionKnockout miceGR signalingNuclear hormone receptorsPharmacological modulationHormone receptorsSevere diseaseAdipose tissueTissue levelsDecay corrected radiochemical yieldMiceHistorical screeningInfluences of early‐life stress on frontolimbic circuitry: Harnessing a dimensional approach to elucidate the effects of heterogeneity in stress exposure
Cohodes EM, Kitt ER, Baskin‐Sommers A, Gee DG. Influences of early‐life stress on frontolimbic circuitry: Harnessing a dimensional approach to elucidate the effects of heterogeneity in stress exposure. Developmental Psychobiology 2020, 63: 153-172. PMID: 32227350, DOI: 10.1002/dev.21969.Peer-Reviewed Original ResearchConceptsEarly life stressFrontolimbic circuitryStress exposurePhysical health problemsEffects of stressCircuit maturationGlucocorticoid receptorHealth problemsMajority of studiesMental healthExposure influencePsychobiological effectsDimensional approachEarly experienceDifferential outcomesOutcomesSubsequent vulnerabilityRiskVast heterogeneityExposureInnervationCircuitryBrainSeverityCaregiversEndothelial 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
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