2025
Inhibition of epithelial cell YAP-TEAD/LOX signaling attenuates pulmonary fibrosis in preclinical models
Wagner D, Alsafadi H, Mitash N, Justet A, Hu Q, Pineda R, Staab-Weijnitz C, Korfei M, Gvazava N, Wannemo K, Onwuka U, Mozurak M, Estrada-Bernal A, Cala-Garcia J, Mutze K, Costa R, Bölükbas D, Stegmayr J, Skronska-Wasek W, Klee S, Ota C, Baarsma H, Wang J, Sembrat J, Hilgendorff A, Ding J, Günther A, Chambers R, Rosas I, de Langhe S, Kaminski N, Lehmann M, Eickelberg O, Königshoff M. Inhibition of epithelial cell YAP-TEAD/LOX signaling attenuates pulmonary fibrosis in preclinical models. Nature Communications 2025, 16: 7099. PMID: 40753090, PMCID: PMC12318044, DOI: 10.1038/s41467-025-61795-x.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAlveolar Epithelial CellsAnimalsCell Cycle ProteinsDisease Models, AnimalDNA-Binding ProteinsExtracellular MatrixFemaleHumansIdiopathic Pulmonary FibrosisLungMaleMiceMice, Inbred C57BLProtein-Lysine 6-OxidaseSignal TransductionTranscription FactorsVerteporfinYAP-Signaling ProteinsConceptsIdiopathic pulmonary fibrosisAlveolar typePulmonary fibrosisIdiopathic pulmonary fibrosis patientsAlveolar type II cellsFibrosis in vivoLung fibrosis in vivoExcessive extracellular matrix depositionType II cellsExcessive extracellular matrix productionPreclinical modelsExtracellular matrix depositionDisease progressionPotential therapiesTissue ex vivoYAP inhibitionCrosslinking of extracellular matrixII cellsLethal diseaseExtracellular matrix productionActive YAPFibrosisMatrix depositionInhibitionDisease
2023
Activation of KrasG12D in Subset of Alveolar Type II Cells Enhances Cellular Plasticity in Lung Adenocarcinoma
Chaudhary P, Xu X, Wang G, Hoj J, Rampersad R, Asselin-Labat M, Ting S, Kim W, Tamayo P, Pendergast A, Onaitis M. Activation of KrasG12D in Subset of Alveolar Type II Cells Enhances Cellular Plasticity in Lung Adenocarcinoma. Cancer Research Communications 2023, 3: 2400-2411. PMID: 37882674, PMCID: PMC10668634, DOI: 10.1158/2767-9764.crc-22-0408.Peer-Reviewed Original ResearchConceptsType II cellsLung adenocarcinomaDual-positive cellsII cellsKRAS-mutant lung adenocarcinomaDevelopment of novel targeted therapeuticsTumor-initiating cellsNotch signalingAlveolar type II cellsNovel targeted therapeuticsCell of originThree-dimensional organoid culturesSOX2 upregulationKras activationAdenocarcinomaMouse modelTherapeutic strategiesProliferation of cellsGain-of-functionRNA sequencing analysisTransplantation studiesCellular plasticityOrganoid culturesSOX2 levelsNotch pathwayAlveolar type II epithelial cell FASN maintains lipid homeostasis in experimental COPD
Fan L, McConn K, Plataki M, Kenny S, Williams N, Kim K, Quirke J, Chen Y, Sauler M, Möbius M, Chung K, Gomez E, Choi A, Xu J, Cloonan S. Alveolar type II epithelial cell FASN maintains lipid homeostasis in experimental COPD. JCI Insight 2023, 8: e163403. PMID: 37606038, PMCID: PMC10543729, DOI: 10.1172/jci.insight.163403.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseAEC2 cellsFatty acid synthaseCigarette smokeExperimental chronic obstructive pulmonary diseaseBronchoalveolar lavage fluid neutrophilsLipid metabolismDisease-chronic obstructive pulmonary diseaseObstructive pulmonary diseaseAlveolar epithelial type II cellsEpithelial type II cellsType II cellsCOPD developmentPulmonary diseaseAirspace enlargementBALF proteinLipogenesis enzymesFerroptosis markersHigh-throughput lipidomic analysisSurfactant phospholipidsMiceSurfactant synthesisLipid homeostasisII cellsCell function
2022
FGF19 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits Lung Fibrosis in Mice.
Justet A, Ghanem M, Boghanim T, Hachem M, Vasarmidi E, Jaillet M, Vadel A, Joannes A, Mordant P, Bonniaud P, Kolb M, Ling L, Cazes A, Mal H, Mailleux A, Crestani B. FGF19 Is Downregulated in Idiopathic Pulmonary Fibrosis and Inhibits Lung Fibrosis in Mice. American Journal Of Respiratory Cell And Molecular Biology 2022, 67: 173-187. PMID: 35549849, DOI: 10.1165/rcmb.2021-0246oc.Peer-Reviewed Original ResearchConceptsIdiopathic pulmonary fibrosisLung collagen contentLung fibrosisFGF19 concentrationsBAL fluidPulmonary fibrosisControl subjectsFibrosis markersMediator expressionFibrotic lung disordersPrimary human lung fibroblastsAlveolar type II cellsDecreased liver fibrosisInhibit lung fibrosisPlasma of patientsBim protein expressionInhibition of JNK phosphorylationCollagen contentType II cellsHuman lung fibroblastsAntifibrotic propertiesFibrotic phaseLung diseaseLung disordersLiver fibrosisCharacterization of the COPD alveolar niche using single-cell RNA sequencing
Sauler M, McDonough JE, Adams TS, Kothapalli N, Barnthaler T, Werder RB, Schupp JC, Nouws J, Robertson MJ, Coarfa C, Yang T, Chioccioli M, Omote N, Cosme C, Poli S, Ayaub EA, Chu SG, Jensen KH, Gomez JL, Britto CJ, Raredon MSB, Niklason LE, Wilson AA, Timshel PN, Kaminski N, Rosas IO. Characterization of the COPD alveolar niche using single-cell RNA sequencing. Nature Communications 2022, 13: 494. PMID: 35078977, PMCID: PMC8789871, DOI: 10.1038/s41467-022-28062-9.Peer-Reviewed Original ResearchConceptsSingle-cell RNA sequencingRNA sequencingCell-specific mechanismsChronic obstructive pulmonary diseaseAdvanced chronic obstructive pulmonary diseaseTranscriptomic network analysisSingle-cell RNA sequencing profilesCellular stress toleranceAberrant cellular metabolismStress toleranceRNA sequencing profilesTranscriptional evidenceCellular metabolismAlveolar nicheSequencing profilesHuman alveolar epithelial cellsChemokine signalingAlveolar epithelial type II cellsObstructive pulmonary diseaseSitu hybridizationType II cellsEpithelial type II cellsSequencingCOPD pathobiologyHuman lung tissue samples
2020
Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics
Blumental-Perry A, Jobava R, Bederman I, Degar A, Kenche H, Guan B, Pandit K, Perry N, Molyneaux N, Wu J, Prendergas E, Ye Z, Zhang J, Nelson C, Ahangari F, Krokowski D, Guttentag S, Linden P, Townsend D, Miron A, Kang M, Kaminski N, Perry Y, Hatzoglou M. Retrograde signaling by a mtDNA-encoded non-coding RNA preserves mitochondrial bioenergetics. Communications Biology 2020, 3: 626. PMID: 33127975, PMCID: PMC7603330, DOI: 10.1038/s42003-020-01322-4.Peer-Reviewed Original ResearchConceptsMitochondrial genomeNuclear-encoded genesCell type-specific mannerNon-coding RNASteady-state transcriptionMitochondrial energy metabolismControl regionPositive regulationMitochondrial bioenergeticsMitochondria stressMitochondrial functionSpecific mannerAlveolar epithelial type II cellsEnergy metabolismType II cellsEpithelial type II cellsGenomePhysiological stressRNAII cellsCellsMouse lungTranscriptionGenesMitochondria
2019
miR-200 family members reduce senescence and restore idiopathic pulmonary fibrosis type II alveolar epithelial cell transdifferentiation
Moimas S, Salton F, Kosmider B, Ring N, Volpe MC, Bahmed K, Braga L, Rehman M, Vodret S, Graziani ML, Wolfson MR, Marchetti N, Rogers TJ, Giacca M, Criner GJ, Zacchigna S, Confalonieri M. miR-200 family members reduce senescence and restore idiopathic pulmonary fibrosis type II alveolar epithelial cell transdifferentiation. ERJ Open Research 2019, 5: 00138-2019. PMID: 31857992, PMCID: PMC6911923, DOI: 10.1183/23120541.00138-2019.Peer-Reviewed Original ResearchIdiopathic pulmonary fibrosisMiR-200 family membersEpithelial-mesenchymal transitionATII cellsEMT markersATI cellsMarker expressionFamily membersRegenerative potentialAlveolar type II cellsType II cellsIPF patientsSenescence marker expressionIPF lungsMiR-200 familyPulmonary fibrosisEpithelial cell transdifferentiationCell markersImpaired expressionFamilial casesCell transdifferentiationII cellsSenescent phenotypeMicroRNA effectsTransdifferentiation
2012
Characterization of Type I and Type II nNOS-Expressing Interneurons in the Barrel Cortex of Mouse
Perrenoud Q, Geoffroy H, Gauthier B, Rancillac A, Alfonsi F, Kessaris N, Rossier J, Vitalis T, Gallopin T. Characterization of Type I and Type II nNOS-Expressing Interneurons in the Barrel Cortex of Mouse. Frontiers In Neural Circuits 2012, 6: 36. PMID: 22754499, PMCID: PMC3386492, DOI: 10.3389/fncir.2012.00036.Peer-Reviewed Original ResearchType II neuronsVasoactive intestinal peptideType I neuronsMedial ganglionic eminenceNeuronal nitric oxide synthaseDeep layer neuronsI neuronsCaudal ganglionic eminenceBarrel cortexGanglionic eminenceLayers II/IIIExpression of parvalbuminNitric oxide synthaseWhole-cell recordingsType IType II cellsNNOS immunohistochemistryDorsal preoptic areaGABAergic neuronsIntestinal peptideOxide synthasePreoptic areaBiocytin labelingSomatostatinEx vivo
2010
Role of Breast Regression Protein–39 in the Pathogenesis of Cigarette Smoke–Induced Inflammation and Emphysema
Matsuura H, Hartl D, Kang MJ, Dela Cruz CS, Koller B, Chupp GL, Homer RJ, Zhou Y, Cho WK, Elias JA, Lee CG. Role of Breast Regression Protein–39 in the Pathogenesis of Cigarette Smoke–Induced Inflammation and Emphysema. American Journal Of Respiratory Cell And Molecular Biology 2010, 44: 777-786. PMID: 20656949, PMCID: PMC3135840, DOI: 10.1165/rcmb.2010-0081oc.Peer-Reviewed Original ResearchConceptsChronic obstructive pulmonary diseaseBRP-39/YKLBreast regression protein 39YKL-40BRP-39Alveolar destructionCigarette smokeChitinase-like protein YKL-40Emphysematous alveolar destructionLungs of CSObstructive pulmonary diseaseProtein YKL-40Excessive inflammatory responseAirway epithelial cellsAlveolar type II cellsNull mutant miceProtein 39Epithelial cell apoptosisType II cellsCurrent smokersPulmonary diseaseBronchoalveolar lavageTissue inflammationEmphysematous destructionSerum concentrations
2003
Pulmonary surfactant secretion in briefly cultured mouse type II cells
Gobran LI, Rooney SA. Pulmonary surfactant secretion in briefly cultured mouse type II cells. American Journal Of Physiology - Lung Cellular And Molecular Physiology 2003, 286: l331-l336. PMID: 14565945, DOI: 10.1152/ajplung.00334.2003.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAdenosine-5'-(N-ethylcarboxamide)AnimalsBronchodilator AgentsCarcinogensCells, CulturedFemaleIonomycinIonophoresLungMiceMice, Inbred C57BLPulmonary Surfactant-Associated Protein BPulmonary Surfactant-Associated Protein CTerbutalineTetradecanoylphorbol AcetateUridine TriphosphateVasodilator AgentsConceptsType II cellsII cellsSurfactant secretionRat type II cellsReceptor null miceStrains of miceSecretion of phosphatidylcholinePulmonary surfactant secretionFVB miceNull miceMiceSecretionSurfactant proteinsPhosphatidylcholine secretionTerbutalineSurfactant secretagoguesIonomycinCellsLittle informationSecretion of SPTPAResponseUTPC57BL/6Agonists
2000
Expression of Thyroid Transcription Factor-1 in Congenital Cystic Adenomatoid Malformation of the Lung
Morotti R, Gutierrez M, Askin F, Profitt S, Wert S, Whitsett J, Greco M. Expression of Thyroid Transcription Factor-1 in Congenital Cystic Adenomatoid Malformation of the Lung. Pediatric And Developmental Pathology 2000, 3: 455-461. PMID: 10890930, DOI: 10.1007/s100240010092.Peer-Reviewed Original ResearchConceptsCongenital cystic adenomatoid malformationCCAM type 1TTF-1 expressionCystic adenomatoid malformationThyroid transcription factor-1Gestational ageTTF-1Type 1Adenomatoid malformationTranscription factor 1Fetal lungAlveolar cell markersBasal cellsEpithelial cellsWeeks gestational ageTTF-1 stainingType 4Factor 1Bronchiolar basal cellsDistal air spacesAlveolar type II cellsType I cellsEarly lung developmentType II cellsCCAM casesActivation of surfactant protein‐B transcription: Signaling through the SP‐A receptor utilizing the PI3 kinase pathway
Strayer D, Korutla L. Activation of surfactant protein‐B transcription: Signaling through the SP‐A receptor utilizing the PI3 kinase pathway. Journal Of Cellular Physiology 2000, 184: 229-238. PMID: 10867648, DOI: 10.1002/1097-4652(200008)184:2<229::aid-jcp11>3.0.co;2-x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedDNA-Binding ProteinsFemaleGlycoproteinsHepatocyte Nuclear Factor 3-alphaLungNuclear ProteinsPhosphatidylinositol 3-KinasesPromoter Regions, GeneticProtein IsoformsProteolipidsPulmonary Surfactant-Associated Protein APulmonary Surfactant-Associated ProteinsPulmonary SurfactantsRatsReceptors, Cell SurfaceThyroid Nuclear Factor 1Transcription FactorsTranscription, GeneticConceptsSP-B promoterSP-B transcriptionPI3-kinaseHNF-3Consensus recognition elementSurfactant proteinsPI3-kinase pathwaySP-A receptorGel shift analysisCell transcriptional activityKinase localizationCellular functionsInteraction of SPTranscription factorsCell biologyNuclear localizationPlasma membraneKinase pathwayTranscriptional activityTranscriptionProteinSpCognate receptorsPromoterType II cells
1999
SP‐A as a cytokine: Surfactant protein‐A–regulated transcription of surfactant proteins and other genes
Korutla L, Strayer D. SP‐A as a cytokine: Surfactant protein‐A–regulated transcription of surfactant proteins and other genes. Journal Of Cellular Physiology 1999, 178: 379-386. PMID: 9989784, DOI: 10.1002/(sici)1097-4652(199903)178:3<379::aid-jcp12>3.0.co;2-c.Peer-Reviewed Original ResearchMeSH KeywordsActinsAnimalsCarrier ProteinsCells, CulturedFemaleGene Expression RegulationGenes, fosGenes, junMacrophages, PeritonealProteolipidsPulmonary AlveoliPulmonary Surfactant-Associated Protein APulmonary Surfactant-Associated ProteinsPulmonary SurfactantsRatsRats, Sprague-DawleyRNA, MessengerTranscription, GeneticConceptsType II cellsSurfactant secretionProtein gene transcriptionSurfactant proteinsSurfactant gene expressionOverall transcript levelsC-fos transcriptionSP-A receptorII cellsSP-C mRNA levelsHost antimicrobial defenseSurfactant proteins SPMRNA levelsTranscript stabilityGene transcriptionSP-A effectsTranscript levelsGene expressionTranscriptionC-JunAlveolar type II cellsNew transcriptionSurfactant-associated proteinsSpProtein
1997
Surfactant protein-A receptor-mediated inhibition of calcium signaling in alveolar type II cells.
Strayer D, Korutla L, Thomas A. Surfactant protein-A receptor-mediated inhibition of calcium signaling in alveolar type II cells. Receptors & Signal Transduction 1997, 7: 111-20. PMID: 9392439.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsBiological TransportCalciumIonomycinMalePhospholipidsProteolipidsPulmonary AlveoliPulmonary Surfactant-Associated Protein APulmonary Surfactant-Associated ProteinsPulmonary SurfactantsRatsRats, Sprague-DawleyReceptors, Cell SurfaceSignal TransductionThapsigarginConceptsReceptor-mediated inhibitionType II cellsII cellsSP-A receptorSurfactant proteinsType II alveolar cellsReceptor-mediated mechanismAlveolar type II cellsCell membrane receptorsQuantitative fluorescence microscopyAbsence of SPMembrane Ca channelsAction of SPFura-2Membrane receptorsCa storesBiphasic increaseIntracellular storesAlveolar cellsElicit Ca2Physiologic regulatorCalcium ionophoreCa channelsCell membraneIntracellular Ca
1989
Two pharmacological classes of quisqualate-induced electrical responses in rat retinal ganglion cells in vitro
Aizenman E, Karschin A, Lipton S. Two pharmacological classes of quisqualate-induced electrical responses in rat retinal ganglion cells in vitro. European Journal Of Pharmacology 1989, 174: 9-22. PMID: 2575535, DOI: 10.1016/0014-2999(89)90868-6.Peer-Reviewed Original ResearchConceptsRetinal ganglion cellsRat retinal ganglion cellsGanglion cellsType I cellsPharmacological classesExcitatory amino acid agonistsAmino acid agonistsI cellsType II cellsType III cellsQuisqualate responseCell typesAMPA responsesFurther pharmacological manipulationPharmacological manipulationPharmacological propertiesPatch electrodeII cellsIII cellsAgonistsAntagonistElicited responsesAMPAType IICellsGABAA/benzodiazepine receptor-like immunoreactivity in rat and monkey cerebellum
Meinecke D, Tallman J, Rakic P. GABAA/benzodiazepine receptor-like immunoreactivity in rat and monkey cerebellum. Brain Research 1989, 493: 303-319. PMID: 2548668, DOI: 10.1016/0006-8993(89)91165-7.Peer-Reviewed Original ResearchConceptsReceptor-like immunoreactivityGABAA/benzodiazepine receptorGolgi type II cellsType II cellsAxon terminalsBasket cellsBenzodiazepine receptorsCerebellar cortexCortical layersII cellsMonkey cerebellumUnlabeled axon terminalsCytoplasm of neuronsMossy fiber terminalsDeep cerebellar nucleiImmunoreactive dendritesSymmetric synapsesImmunostained neuronsInhibitory circuitsLabel neuronsGlial cellsNeuronal typesFiber terminalsGranule cellsStellate cells
1985
Delayed Pulmonary Maturation in the Fetus of the Streptozotocin-Diabetic Rat
Gewolb I, Rooney S, Barrett C, Ingleson L, Light D, Wilson C, Smith G, Gross I, Warshaw J. Delayed Pulmonary Maturation in the Fetus of the Streptozotocin-Diabetic Rat. Experimental Lung Research 1985, 8: 141-151. PMID: 4029093, DOI: 10.3109/01902148509057518.Peer-Reviewed Original ResearchConceptsStreptozotocin-diabetic ratsDiabetic groupPulmonary maturationDay 21Lung developmentDelayed pulmonary maturationAlveolar lining cellsEffects of hyperglycemiaFetal lung developmentDays of gestationObserved developmental delayType II cellsControl lungsMaturational delayCholinephosphate cytidylyltransferase activityIntravenous injectionRat gestationDiabetic fetusesLining cellsDay 22Day 20FetusesActivity of enzymesDevelopmental delayDecreased number
1981
Organotypic Culture of Fetal Rat Lung: Evaluation and Comparison with Organ Culture1–3
Gross I, Freedman R, Wilson C, Lindsey S. Organotypic Culture of Fetal Rat Lung: Evaluation and Comparison with Organ Culture1–3. American Journal Of Respiratory And Critical Care Medicine 1981, 123: 313-9. PMID: 7224342, DOI: 10.1164/arrd.1981.123.3.313.Peer-Reviewed Original Research
1980
The Influence of Hormones on the Biochemical Development of Fetal Rat Lung in Organ Culture. II. Insulin
Gross I, Walker Smith G, Wilson C, Maniscalco W, Ingleson L, Brehier A, Rooney S. The Influence of Hormones on the Biochemical Development of Fetal Rat Lung in Organ Culture. II. Insulin. Pediatric Research 1980, 14: 834-838. PMID: 6995921, DOI: 10.1203/00006450-198006000-00012.Peer-Reviewed Original ResearchConceptsFetal rat lungRat lungCholine incorporationSignificant decreasePhospholipid fractionInfluence of insulinEffect of insulinInfluence of hormonesPercentage of radioactivityType II cellsLung cell growthLung cell differentiationLung maturationOrgan culture systemInsulin treatmentMorphologic evidencePhospholipid radioactivityInsulinMorphologic maturationSurfactant phospholipidsGlycogen contentII cellsOrgan cultureBiochemical developmentLamellar bodies
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