2023
Endothelial 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 disease
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 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 geneMetabolismCellsLoss 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
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-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
microRNA Crosstalk Influences Epithelial-to-Mesenchymal, Endothelial-to-Mesenchymal, and Macrophage-to-Mesenchymal Transitions in the Kidney
Srivastava SP, Hedayat A, Kanasaki K, Goodwin JE. microRNA Crosstalk Influences Epithelial-to-Mesenchymal, Endothelial-to-Mesenchymal, and Macrophage-to-Mesenchymal Transitions in the Kidney. Frontiers In Pharmacology 2019, 10: 904. PMID: 31474862, PMCID: PMC6707424, DOI: 10.3389/fphar.2019.00904.Peer-Reviewed Original ResearchMesenchymal transitionExcess extracellular matrixDiverse biological processesGrowth factor β receptorNon-coding nucleotidesMiR-29Fibrotic disease statesRole of microRNAsEndothelial cell homeostasisEpithelial cellsMicroRNA biosynthesisMesenchymal programGrowth factor βAberrant regulationEndothelial cellsCrosstalk mechanismsCell homeostasisBiological processesM2 phenotype macrophagesDipeptidyl peptidase-4Extracellular matrixBone marrow-derived monocytesIntegrin β1Novel therapeutic targetMesenchymal activation
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 genetics