2016
Inhibition of Regulatory-Associated Protein of Mechanistic Target of Rapamycin Prevents Hyperoxia-Induced Lung Injury by Enhancing Autophagy and Reducing Apoptosis in Neonatal Mice
Sureshbabu A, Syed M, Das P, Janér C, Pryhuber G, Rahman A, Andersson S, Homer RJ, Bhandari V. Inhibition of Regulatory-Associated Protein of Mechanistic Target of Rapamycin Prevents Hyperoxia-Induced Lung Injury by Enhancing Autophagy and Reducing Apoptosis in Neonatal Mice. American Journal Of Respiratory Cell And Molecular Biology 2016, 55: 722-735. PMID: 27374190, PMCID: PMC5105179, DOI: 10.1165/rcmb.2015-0349oc.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAdaptor Proteins, Signal TransducingAlveolar Epithelial CellsAnimalsAnimals, NewbornApoptosisAutophagyBronchopulmonary DysplasiaCell LineFemaleHumansHyperoxiaHypertension, PulmonaryHypertrophy, Right VentricularInfant, NewbornLungMiceMicrotubule-Associated ProteinsNaphthyridinesPhenotypeRegulatory-Associated Protein of mTORTime FactorsTumor Suppressor Protein p53ConceptsAcute lung injuryBronchopulmonary dysplasiaLung injuryWild-type miceMechanistic targetRegulatory-Associated ProteinLysosomal-associated membrane protein 1Apoptotic cell deathFetal type II alveolar epithelial cellsMouse lungRole of autophagyHyperoxia-Induced Lung InjuryLight chain 3Activation of autophagyType II alveolar epithelial cellsRespiratory distress syndromeMembrane protein 1Developmental lung diseaseUseful therapeutic targetNeonatal mouse lungAlveolar epithelial cellsPharmacological inhibitorsTreatment of hyperoxiaCell deathAutophagic flux
2015
Conditional overexpression of TGFβ1 promotes pulmonary inflammation, apoptosis and mortality via TGFβR2 in the developing mouse lung
Sureshbabu A, Syed MA, Boddupalli CS, Dhodapkar MV, Homer RJ, Minoo P, Bhandari V. Conditional overexpression of TGFβ1 promotes pulmonary inflammation, apoptosis and mortality via TGFβR2 in the developing mouse lung. Respiratory Research 2015, 16: 4. PMID: 25591994, PMCID: PMC4307226, DOI: 10.1186/s12931-014-0162-6.Peer-Reviewed Original ResearchMeSH KeywordsAcute Lung InjuryAlveolar Epithelial CellsAnimalsAnimals, NewbornApoptosisDisease Models, AnimalGenotypeHumansHyperoxiaLungMice, Inbred C57BLMice, KnockoutMice, TransgenicPhenotypePneumoniaProtein Serine-Threonine KinasesReceptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSignal TransductionTime FactorsTransforming Growth Factor beta1Up-RegulationConceptsImpaired alveolarizationBronchopulmonary dysplasiaAlveolar epithelial cellsPulmonary inflammationPulmonary phenotypeMouse lungAcute lung injuryType II alveolar epithelial cellsApoptotic cell deathCell deathNewborn mouse lungPotential therapeutic strategyGrowth factor betaNull mutant miceLung injuryImproved survivalNeonatal mortalityMonocyte infiltrationAbnormal alveolarizationAngiogenic mediatorsInflammatory signalsTGFβ1 expressionTherapeutic strategiesInflammatory macrophagesLung morphometry
2013
Hyperoxia and Interferon-γ–Induced Injury in Developing Lungs Occur via Cyclooxygenase-2 and the Endoplasmic Reticulum Stress–Dependent Pathway
Choo-Wing R, Syed MA, Harijith A, Bowen B, Pryhuber G, Janér C, Andersson S, Homer RJ, Bhandari V. Hyperoxia and Interferon-γ–Induced Injury in Developing Lungs Occur via Cyclooxygenase-2 and the Endoplasmic Reticulum Stress–Dependent Pathway. American Journal Of Respiratory Cell And Molecular Biology 2013, 48: 749-757. PMID: 23470621, PMCID: PMC3727872, DOI: 10.1165/rcmb.2012-0381oc.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBronchopulmonary DysplasiaCelecoxibCell DeathCyclooxygenase 2Cyclooxygenase 2 InhibitorsEndoplasmic Reticulum StressHumansHyperoxiaImmunohistochemistryInfant, NewbornInterferon-gammaLungMiceMice, Inbred C57BLMice, TransgenicPyrazolesRNA, Small InterferingSulfonamidesTranscription Factor CHOPConceptsBronchopulmonary dysplasiaCyclooxygenase-2Endoplasmic reticulum stress-dependent pathwaysER stress pathway activationPathway mediatorsHuman bronchopulmonary dysplasiaFinal common pathwayAlveolar epithelial cellsImpaired alveolarizationStress pathway activationCOX2 inhibitionMurine modelMurine lungClinical relevanceIFNVivo modelHyperoxiaLungHuman lungPathway activationCHOP siRNAStress-dependent pathwaysInjuryEpithelial cellsCommon pathway
2012
Increased Hyperoxia-Induced Lung Injury in Nitric Oxide Synthase 2 Null Mice Is Mediated via Angiopoietin 2
Bhandari V, Choo-Wing R, Harijith A, Sun H, Syed MA, Homer RJ, Elias JA. Increased Hyperoxia-Induced Lung Injury in Nitric Oxide Synthase 2 Null Mice Is Mediated via Angiopoietin 2. American Journal Of Respiratory Cell And Molecular Biology 2012, 46: 668-676. PMID: 22227562, PMCID: PMC3359903, DOI: 10.1165/rcmb.2011-0074oc.Peer-Reviewed Original ResearchConceptsHyperoxic acute lung injuryNOS/nitric oxideNitric oxideLung injuryAngiopoietin-2Pathogenesis of HALIAlveolar-capillary protein leakAcute respiratory distress syndromeHyperoxia-Induced Lung InjuryAcute lung injuryRespiratory distress syndromeImportant protective roleCell deathBronchopulmonary dysplasiaDistress syndromeSupplemental oxygenNb miceProtein leakTissue injuryProtective roleNewbornsNull micePremature deathAdult controlsAng2
2011
A Role for Matrix Metalloproteinase 9 in IFNγ-Mediated Injury in Developing Lungs
Harijith A, Choo-Wing R, Cataltepe S, Yasumatsu R, Aghai ZH, Janér J, Andersson S, Homer RJ, Bhandari V. A Role for Matrix Metalloproteinase 9 in IFNγ-Mediated Injury in Developing Lungs. American Journal Of Respiratory Cell And Molecular Biology 2011, 44: 621-630. PMID: 21216975, PMCID: PMC3095982, DOI: 10.1165/rcmb.2010-0058oc.Peer-Reviewed Original ResearchConceptsBronchopulmonary dysplasiaHuman bronchopulmonary dysplasiaLung architectureRole of IFNγMatrix metalloproteinase-9Caspase-3Final common pathwayMatrix metalloproteinases 2Downstream targetsImpaired alveolarizationLung injuryChemokine ligandMetalloproteinase-9IFNγ mRNAAngiopoietin-2Murine modelLittermate controlsPulmonary phenotypeMurine lungClinical relevanceLung phenotypeAngiopoietin-1IFNγMetalloproteinases 2Lung
2008
Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung
Bhandari V, Choo-Wing R, Lee CG, Yusuf K, Nedrelow JH, Ambalavanan N, Malkus H, Homer RJ, Elias JA. Developmental Regulation of NO-Mediated VEGF-Induced Effects in the Lung. American Journal Of Respiratory Cell And Molecular Biology 2008, 39: 420-430. PMID: 18441284, PMCID: PMC2551703, DOI: 10.1165/rcmb.2007-0024oc.Peer-Reviewed Original ResearchMeSH KeywordsAmniotic FluidAnimalsAnimals, NewbornBronchopulmonary DysplasiaCapillary PermeabilityFemaleHemorrhageHumansHyperoxiaInfant, NewbornLungLung DiseasesMiceMice, TransgenicNitric OxidePregnancyPulmonary SurfactantsRespiratory Distress Syndrome, NewbornTracheaVascular Endothelial Growth Factor AConceptsVascular endothelial growth factorVEGF levelsLung developmentNitric oxide mediationNO-dependent mechanismAdult murine lungPotential clinical benefitTransgenic murine modelSignificant differencesEndothelial growth factorBronchopulmonary dysplasiaLung injuryPulmonary hemorrhageCytokine responsesClinical benefitNeonatal lungHuman neonatesMurine modelMurine lungMature lungLungPathologic conditionsAdult lungSurfactant phospholipidsExtravascular effects
2006
Hyperoxia causes angiopoietin 2–mediated acute lung injury and necrotic cell death
Bhandari V, Choo-Wing R, Lee CG, Zhu Z, Nedrelow JH, Chupp GL, Zhang X, Matthay MA, Ware LB, Homer RJ, Lee PJ, Geick A, de Fougerolles AR, Elias JA. Hyperoxia causes angiopoietin 2–mediated acute lung injury and necrotic cell death. Nature Medicine 2006, 12: 1286-1293. PMID: 17086189, PMCID: PMC2768268, DOI: 10.1038/nm1494.Peer-Reviewed Original ResearchConceptsAcute lung injuryHyperoxic acute lung injuryLung injuryPulmonary edemaEpithelial necrosisAlveolar edema fluidSiRNA-treated miceCell deathLung epithelial cellsEndothelial cell apoptosisBronchopulmonary dysplasiaVascular leakAngiopoietin-2Edema fluidOxidant injuryAng2 expressionHyperoxiaAng2Vascular regressionBlood vesselsCell apoptosisInjuryNecrotic cell deathEpithelial cellsCell death pathways