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 regulation
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 miceEndothelial 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
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
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
2013
Abdominal distention and renal failure in a neonate
Bedri B, Goodwin JE. Abdominal distention and renal failure in a neonate. BMJ Case Reports 2013, 2013: bcr2012007955. PMID: 23429016, PMCID: PMC3604299, DOI: 10.1136/bcr-2012-007955.Peer-Reviewed Original ResearchConceptsAbdominal distentionRenal failureSevere unilateral hydronephrosisSignificant abdominal distentionPosterior urethral valvesTerm male neonateHospital dischargeUnilateral hydronephrosisUrethral valvesMale neonatePrenatal careDefinitive diagnosisMetabolic acidosisEchogenic kidneysDistentionNeonatesCystourethrogramHydronephrosisFailureDerangementAcidosisPediatriciansKidneyLab testsDiagnosisA 7-year-old boy with renal insufficiency and proteinuria after stem cell transplant for T-cell acute lymphoblastic leukemia
Goodwin JE, Palmer M, Pashankar F, Tufro A, Moeckel G. A 7-year-old boy with renal insufficiency and proteinuria after stem cell transplant for T-cell acute lymphoblastic leukemia. Clinical Nephrology 2013, 82: 205-210. PMID: 23391318, PMCID: PMC6990651, DOI: 10.5414/cn107767.Peer-Reviewed Original ResearchConceptsStem cell transplantHematopoietic stem cell transplantCell transplantRenal insufficiencyKidney biopsyPediatric patientsNephrotic syndromeExtensive foot process effacementAbnormal lymphocyte responsesT-cell acute lymphoblastic leukemiaChronic kidney diseaseChronic interstitial nephritisAcute lymphoblastic leukemiaPre-conditioning regimensFoot process effacementHost diseaseImmunosuppressive therapyRenal failureInterstitial nephritisLymphocyte responsesCommon sequelaeInterstitial infiltratesProphylactic medicationKidney diseaseLikely multifactorial
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
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
A 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