2025
MAP Kinase Phosphatase-5 Deficiency Improves Endurance Exercise Capacity
Perales J, Lawan A, Bajpeyi S, Han S, Bennett A, Min K. MAP Kinase Phosphatase-5 Deficiency Improves Endurance Exercise Capacity. Cells 2025, 14: 410. PMID: 40136658, PMCID: PMC11941502, DOI: 10.3390/cells14060410.Peer-Reviewed Original ResearchConceptsResponse to aerobic exerciseEndurance exercise capacityAerobic exerciseExercise capacityProgressive exercise stress testExercise training programEnhance endurance performanceCardiac adaptationPhysiological cardiac adaptationExercise stress testExercise habituationEndurance performanceRunning distanceCardiovascular healthTreadmill exerciseTraining programExerciseImproving cardiovascular functionSedentary miceTreadmillCardiac muscleEnduranceMitogen-activated protein kinaseMuscleStress testDepletion of Fkbp5 Protects Against the Rapid Decline in Ovarian Reserve Induced by Prenatal Stress in Female Offspring of Wild-Type Mice
Moore M, Cetinkaya-Un B, Sarkar P, Kayisli U, Semerci-Gunay N, Teng M, Lockwood C, Guzeloglu-Kayisli O. Depletion of Fkbp5 Protects Against the Rapid Decline in Ovarian Reserve Induced by Prenatal Stress in Female Offspring of Wild-Type Mice. International Journal Of Molecular Sciences 2025, 26: 2471. PMID: 40141115, PMCID: PMC11942629, DOI: 10.3390/ijms26062471.Peer-Reviewed Original ResearchConceptsOvarian reservePrenatal stressFKBP51 levelsPostnatal ovarian functionReduced ovarian reserveOvarian steroid synthesisWild-type miceMaternal restraint stressPrenatal stress groupPrenatally stressed offspringExpression of FKBP51Inhibit glucocorticoidProgesterone receptorTertiary folliclesEmbryonic day 8Granulosa cellsOvarian functionRestraint stressSteroidogenic enzymesMiddle-aged groupOvarian expressionFollicle atresiaPrenatal stress effectsDay 8Steroid synthesisAn atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis
El Bounkari O, Zan C, Yang B, Ebert S, Wagner J, Bugar E, Kramer N, Bourilhon P, Kontos C, Zarwel M, Sinitski D, Milic J, Jansen Y, Kempf W, Sachs N, Maegdefessel L, Ji H, Gokce O, Riols F, Haid M, Gerra S, Hoffmann A, Brandhofer M, Avdic M, Bucala R, Megens R, Willemsen N, Messerer D, Schulz C, Bartelt A, Harm T, Rath D, Döring Y, Gawaz M, Weber C, Kapurniotu A, Bernhagen J. An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis. Nature Communications 2025, 16: 2297. PMID: 40055309, DOI: 10.1038/s41467-025-57540-z.Peer-Reviewed Original ResearchConceptsApoE-/- miceHyperlipidemic apoE-/- miceCoronary artery diseaseDecreased plasma lipid levelsPlasma lipid levelsHepatic lipid accumulationAtherogenic chemokinesFoam-cell formationFLIM-FRET microscopyArtery diseasePlasma concentrationsVascular inflammationInflammatory conditionsMetabolic dysfunctionAtherosclerotic patientsLipid accumulationAdvanced atherosclerosisMyocardial infarctionLipid levelsSuppressed hepatic lipid accumulationAdvanced atherogenesisCarotid plaquesDisease severityIschemic strokeChemokinesHypercholesterolemia-induced LXR signaling in smooth muscle cells contributes to vascular lesion remodeling and visceral function
Zhang H, de Urturi D, Fernández-Tussy P, Huang Y, Jovin D, Zhang X, Huang S, Lek M, da Silva Catarino J, Sternak M, Citrin K, Swirski F, Gustafsson J, Greif D, Esplugues E, Biwer L, Suárez Y, Fernández-Hernando C. Hypercholesterolemia-induced LXR signaling in smooth muscle cells contributes to vascular lesion remodeling and visceral function. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2417512122. PMID: 40035761, PMCID: PMC11912459, DOI: 10.1073/pnas.2417512122.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsSmooth muscle cellsLiver X receptorLesion remodelingMuscle cellsVascular functionArterial media layerContribution of lipid metabolismPhenotypic switchingRegulate vascular toneMonocyte-derived macrophagesLipid metabolismPhenotypic switching of vascular smooth muscle cellsSwitching of vascular smooth muscle cellsNecrotic core areaRegulate vascular functionFoam cell populationVisceral myopathyBladder remodelingAortic atheromaFibrous cap thicknessRemodeling in vivoLipid malabsorptionVascular toneAbundant cell typeSuppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases
Rubinelli L, Manzo O, Sungho J, Del Gaudio I, Bareja R, Marino A, Palikhe S, Di Mauro V, Bucci M, Falcone D, Elemento O, Ersoy B, Diano S, Sasset L, Di Lorenzo A. Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases. Nature Communications 2025, 16: 1968. PMID: 40000621, PMCID: PMC11862206, DOI: 10.1038/s41467-025-56869-9.Peer-Reviewed Original ResearchConceptsNogo-BEndothelial dysfunctionHFD miceCardiometabolic diseasesSphingolipid signalingDevelopment of therapeutic strategiesBioactive sphingolipidsCeramide degradationSphingosine-1-phosphateHepatic glucose productionIn vivo evidenceEndothelial cellsEndothelial specific deletionCeramideBiosynthesisHigh-fat dietPathological implicationsSphingolipidsGlucose productionHFDIn vivoMale miceMetabolic dysfunctionTherapeutic strategiesMetabolic disordersEndothelial SHANK3 regulates tight junctions in the neonatal mouse blood-brain barrier through β-Catenin signaling
Kim Y, Kim M, Kim S, Lee R, Ujihara Y, Marquez-Wilkins E, Jiang Y, Yang E, Kim H, Lee C, Park C, Kim I. Endothelial SHANK3 regulates tight junctions in the neonatal mouse blood-brain barrier through β-Catenin signaling. Nature Communications 2025, 16: 1407. PMID: 39915488, PMCID: PMC11802743, DOI: 10.1038/s41467-025-56720-1.Peer-Reviewed Original ResearchConceptsBlood-brain barrierNeuronal excitabilityB-cateninBarrier functionMouse blood-brain barrierReduced neuronal excitabilityMale mutant miceBlood-brain barrier permeabilityBrain endothelial cellsAutism spectrum disorderNeonatal micePotential therapeutic targetASD risk genesMutant miceTight junctionsImpaired sociabilityPathogenic mechanismsBrain parenchymaEndothelial cellsTherapeutic targetASD pathogenesisSHANK3Adult ageDisabling conditionMiceThe metabolic and cardiovascular effects of amphetamine are partially mediated by the central melanocortin system
Simonds S, Pryor J, Lam B, Dowsett G, Mustafa T, Munder A, Elysee K, Balland E, Cowley L, Yeo G, Lawrence A, Spanswick D, Cowley M. The metabolic and cardiovascular effects of amphetamine are partially mediated by the central melanocortin system. Cell Reports Medicine 2025, 6: 101936. PMID: 39914386, PMCID: PMC11866487, DOI: 10.1016/j.xcrm.2025.101936.Peer-Reviewed Original ResearchConceptsEffects of amphetamineCentral melanocortin systemCardiovascular effectsMelanocortin systemFood intakeInhibition of POMC neuronsAMPH-induced anorexiaMelanocortin 4 receptor-deficientNoradrenergic neurotransmitter systemsHeart rateBrown adipose tissueElevated blood pressureBody weightNoradrenergic inhibitionPOMC neuronsAMPH-inducedSerotonergic activityPresynaptic mechanismsNeurotransmitter systemsMC4R pathwayAmphetamineBlood pressureCardiovascular functionIncreased brown adipose tissueAdipose tissueDeletion of sphingosine 1-phosphate receptor 1 in myeloid cells reduces hepatic inflammatory macrophages and attenuates MASH
Parthasarathy G, Venkatesan N, Sidhu G, Song M, Liao C, Barrow F, Mauer A, Sehrawat T, Nakao Y, Daniel P, Dasgupta D, Pavelko K, Revelo X, Malhi H. Deletion of sphingosine 1-phosphate receptor 1 in myeloid cells reduces hepatic inflammatory macrophages and attenuates MASH. Hepatology Communications 2025, 9: e0613. PMID: 39899672, DOI: 10.1097/hc9.0000000000000613.Peer-Reviewed Original ResearchConceptsMyeloid cellsMonocyte-derived macrophagesHigh-fatLiver injuryProinflammatory monocyte-derived macrophagesReceptor 1Cell-specific knockout miceMass cytometryT cell subsetsSphingosine 1-phosphate receptor 1Cardiometabolic risk factorsS1P receptor 1Accumulation of monocyte-derived macrophagesImmune cell typesWild-typeLiver inflammatory infiltrationGene ontology pathway analysisWild-type controlsDevelopment of steatohepatitisSphingosine 1-phosphateMitogen-activated protein kinase pathwayT cellsIntrahepatic macrophagesInflammatory infiltrateKnockout miceMicroglia modulate the cerebrovascular reactivity through ectonucleotidase CD39
Fu Z, Ganesana M, Hwang P, Tan X, Kinkaid M, Sun Y, Bian E, Weybright A, Chen H, Sol-Church K, Eyo U, Pridans C, Quintana F, Robson S, Kumar P, Venton B, Schaefer A, Kuan C. Microglia modulate the cerebrovascular reactivity through ectonucleotidase CD39. Nature Communications 2025, 16: 956. PMID: 39843911, PMCID: PMC11754601, DOI: 10.1038/s41467-025-56093-5.Peer-Reviewed Original ResearchConceptsCerebral blood flowEctonucleotidases CD39Whisker stimulationResponse to whisker stimulationCerebrovascular reactivityDeletion of CD39Blood flowInjection of adenosine triphosphateModulation of cerebral blood flowRegulation of cerebral blood flowExtracellular adenosine triphosphateInjection of adenosineBorder-associated macrophagesMicroglia repopulationExtracellular adenosineAdenosine triphosphateFemale miceBlood flow anomaliesP2RY12 receptorCo-transmitterMouse modelPharmacological inhibitionCD39MicrogliaMiceGPR55 in the tumor microenvironment of pancreatic cancer controls tumorigenesis
Ristić D, Bärnthaler T, Gruden E, Kienzl M, Danner L, Herceg K, Sarsembayeva A, Kargl J, Schicho R. GPR55 in the tumor microenvironment of pancreatic cancer controls tumorigenesis. Frontiers In Immunology 2025, 15: 1513547. PMID: 39885986, PMCID: PMC11779727, DOI: 10.3389/fimmu.2024.1513547.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaModel of pancreatic ductal adenocarcinomaImmune tumor microenvironmentTumor microenvironmentT cellsKO miceEndocannabinoid systemWT miceTumor growthCD8<sup>+</sup> T cellsG protein-coupled receptor 55Suppress T cell functionCancer cellsMurine pancreatic ductal adenocarcinomaCD3<sup>+</sup> T cellsExpression of PDL1T cell influxImmune cell compositionT cell functionTumor microenvironment cellsMigration of T cellsReduced tumor weightImmune cell populationsT cell activationCell linesChronic Rapamycin Prevents Electrophysiological and Morphological Alterations Produced by Conditional Pten Deletion in Mouse Cortex
Hauptman J, Antonios J, Mathern G, Levine M, Cepeda C. Chronic Rapamycin Prevents Electrophysiological and Morphological Alterations Produced by Conditional Pten Deletion in Mouse Cortex. Cells 2025, 14: 79. PMID: 39851507, PMCID: PMC11764219, DOI: 10.3390/cells14020079.Peer-Reviewed Original ResearchConceptsCortical pyramidal neuronsMice treated with rapamycinGABA releasePTEN deletionWhole-cell patch-clamp recordingsMiniature inhibitory postsynaptic currentsEx vivo slicesNeuronal somatic sizeReduced neuronal firingInhibitory postsynaptic currentsChronic rapamycin treatmentPatch-clamp recordingsIncreased input resistanceInhibitory synaptic inputsDevelopmental brain disordersRapamycin treatmentIncreased membrane capacitanceConditional mouse modelChronic treatmentPostsynaptic currentsClamp recordingsNaive miceSynaptic excitationBrain disordersControl miceTau is a receptor with low affinity for glucocorticoids and is required for glucocorticoid-induced bone loss
Fu W, Chen M, Wang K, Chen Y, Cui Y, Xie Y, Lei Z, Hu W, Sun G, Huang G, He C, Fretz J, Hettinghouse A, Liu R, Cai X, Zhang M, Chen Y, Jiang N, He M, Wiznia D, Xu H, Chen Z, Chen L, Tang K, Zhou H, Liu C. Tau is a receptor with low affinity for glucocorticoids and is required for glucocorticoid-induced bone loss. Cell Research 2025, 35: 23-44. PMID: 39743632, PMCID: PMC11701132, DOI: 10.1038/s41422-024-01016-0.Peer-Reviewed Original ResearchConceptsGC-induced osteoporosisBone lossInflammatory arthritisAdverse effects of dexamethasoneGlucocorticoid-induced bone lossHigh-dose dexamethasoneEffect of dexamethasoneFDA-approved drug librarySynthetic GCTreat inflammatory arthritisImmunosuppressive drugsPrescribed anti-inflammatoryGC receptorCombinatorial administrationSide effectsLow affinityGlucocorticoidOsteoporosisDexamethasoneReceptorsAdverse effectsBinding receptorsAnti-inflammatoryDrug libraryTau deficiency
2024
Heterogeneous Cardiac-Derived and Neural Crest–Derived Aortic Smooth Muscle Cells Exhibit Similar Transcriptional Changes After TGFβ Signaling Disruption
Ren P, Jiang B, Hassab A, Li G, Li W, Assi R, Tellides G. Heterogeneous Cardiac-Derived and Neural Crest–Derived Aortic Smooth Muscle Cells Exhibit Similar Transcriptional Changes After TGFβ Signaling Disruption. Arteriosclerosis Thrombosis And Vascular Biology 2024, 45: 260-276. PMID: 39697172, DOI: 10.1161/atvbaha.124.321706.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaAortic AneurysmCell LineageDisease Models, AnimalGene Expression ProfilingHomeobox Protein Nkx-2.5HumansMaleMarfan SyndromeMiceMice, Inbred C57BLMice, KnockoutMuscle, Smooth, VascularMyocytes, Smooth MuscleMyosin Heavy ChainsNeural CrestPhenotypeReceptor, Transforming Growth Factor-beta Type IIReceptors, Transforming Growth Factor betaSignal TransductionSingle-Cell AnalysisTranscription, GeneticTranscriptomeTransforming Growth Factor betaWnt1 ProteinConceptsSmooth muscle cell clustersSmooth muscle cellsAortic smooth muscle cellsNeural crest-derived smooth muscle cellsCardiac derivativesMurine aortic smooth muscle cellsNeural crest originReceptor deletionAortic rootAdult miceNeural crest progenitorsNKX2-5Proximal aortaTranscriptional changesMouse modelTGFB signalingMuscle cellsConditional deletionAdult human aortaEmbryological originIncreased expressionAnalyzed single-cell transcriptomesTGFB receptorsBasal stateAortic homeostasisInterplay between Netrin-1 and Norrin controls arteriovenous zonation of blood–retina barrier integrity
Furtado J, Geraldo L, Leser F, Bartkowiak B, Poulet M, Park H, Robinson M, Pibouin-Fragner L, Eichmann A, Boyé K. Interplay between Netrin-1 and Norrin controls arteriovenous zonation of blood–retina barrier integrity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2408674121. PMID: 39693351, PMCID: PMC11670198, DOI: 10.1073/pnas.2408674121.Peer-Reviewed Original ResearchConceptsBlood-retina barrierBlood-retina barrier integrityGene expressionScRNA-seqEndothelial cellsNetrin-1 receptor UNC5BNetrin-1Cell gene expression programsSingle-cell RNA sequencingDevelopment of retinal diseasesWnt signaling componentsGene expression programsTight junction proteinsMutant endothelial cellsScaffold proteinTranscriptional activityLoss of functionRNA sequencingRetinal arteriolesRetina endothelial cellsRetinal diseasesHomologue 1Expression programsReceptor UNC5BEndothelial subtypesX-linked deletion of Crossfirre, Firre, and Dxz4 in vivo uncovers diverse phenotypes and combinatorial effects on autosomes
Hasenbein T, Hoelzl S, Smith Z, Gerhardinger C, Gonner M, Aguilar-Pimentel A, Amarie O, Becker L, Calzada-Wack J, Dragano N, da Silva-Buttkus P, Garrett L, Hölter S, Kraiger M, Östereicher M, Rathkolb B, Sanz-Moreno A, Spielmann N, Wurst W, Gailus-Durner V, Fuchs H, Hrabě de Angelis M, Meissner A, Engelhardt S, Rinn J, Andergassen D. X-linked deletion of Crossfirre, Firre, and Dxz4 in vivo uncovers diverse phenotypes and combinatorial effects on autosomes. Nature Communications 2024, 15: 10631. PMID: 39638999, PMCID: PMC11621363, DOI: 10.1038/s41467-024-54673-5.Peer-Reviewed Original ResearchConceptsAutosomal gene regulationRegions genome-wideAllele-specific analysisSex-specific lociLoci in vivoX-linked genesRandom X-chromosome inactivationX-chromosome inactivationSex-specific phenotypesFirre locusGenome-wideIn vivo roleChromatin structureGene regulationX chromosomeEpigenetic featuresDXZ4Epigenetic profilesKnockout studiesLociDiverse phenotypesLncRNA FIRREFunctional roleCombinatorial effectsFIRREEzrin drives adaptation of monocytes to the inflamed lung microenvironment
Gudneppanavar R, Di Pietro C, H Öz H, Zhang P, Cheng E, Huang P, Tebaldi T, Biancon G, Halene S, Hoppe A, Kim C, Gonzalez A, Krause D, Egan M, Gupta N, Murray T, Bruscia E. Ezrin drives adaptation of monocytes to the inflamed lung microenvironment. Cell Death & Disease 2024, 15: 864. PMID: 39613751, PMCID: PMC11607083, DOI: 10.1038/s41419-024-07255-8.Peer-Reviewed Original ResearchConceptsActivation of focal adhesion kinaseExtracellular matrixActin-binding proteinsFocal adhesion kinaseLung extracellular matrixKnock-out mouse modelProtein kinase signalingCortical cytoskeletonLoss of ezrinKinase signalingPlasma membraneCell migrationSignaling pathwayEzrinResponse to lipopolysaccharideTissue-resident macrophagesMouse modelLipopolysaccharideCytoskeletonEzrin expressionLung microenvironmentKinaseMonocyte recruitmentProteinAktCB1R activates the epilepsy-associated protein Go to regulate neurotransmitter release and synaptic plasticity in the cerebellum
Choi J, Acharya R, Lim H, Lee K, Seo J, Yang E, Kim H, Yoon J, Chang D, Kim S, Kim S, Birnbaumer L, Suh-Kim H. CB1R activates the epilepsy-associated protein Go to regulate neurotransmitter release and synaptic plasticity in the cerebellum. Proceedings Of The National Academy Of Sciences Of The United States Of America 2024, 121: e2409773121. PMID: 39602265, PMCID: PMC11626142, DOI: 10.1073/pnas.2409773121.Peer-Reviewed Original ResearchConceptsDepolarization-induced suppression of excitationCannabinoid receptor type 1Synaptic plasticityDepolarization-induced suppressionSuppression of excitationHeterotrimeric Go proteinAbundant G proteinGi/o-coupled receptorsNeurotransmitter releasePresynaptic terminalsReceptor type 1Regulate neurotransmitter releaseBeam balance testBrain synaptosomal fractionsRegulating neurotransmittersMutated animalsMultiple proteinsKO miceProteomic analysisMotor deficitsCB1RCerebellumEpileptic encephalopathyGo proteinsSignaling pathwayHypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer
Robles-Oteíza C, Hastings K, Choi J, Sirois I, Ravi A, Expósito F, de Miguel F, Knight J, López-Giráldez F, Choi H, Socci N, Merghoub T, Awad M, Getz G, Gainor J, Hellmann M, Caron É, Kaech S, Politi K. Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer. Journal Of Experimental Medicine 2024, 222: e20231106. PMID: 39585348, PMCID: PMC11602551, DOI: 10.1084/jem.20231106.Peer-Reviewed Original ResearchConceptsImmune checkpoint inhibitorsNon-small cell lung cancerAcquired resistanceCheckpoint inhibitorsResistant tumorsPatients treated with anti-PD-1/PD-L1 therapyAnti-PD-1/PD-L1 therapyLung cancerResistance to immune checkpoint inhibitorsAssociated with decreased progression-free survivalHypoxia activated pro-drugsTargeting hypoxic tumor regionsTreat non-small cell lung cancerAnti-CTLA-4Anti-PD-1Immune checkpoint inhibitionTumor metabolic featuresProgression-free survivalCell lung cancerResistant cancer cellsHypoxic tumor regionsMHC-II levelsRegions of hypoxiaKnock-outCheckpoint inhibitionUBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling
Harrison A, Yang D, Cahoon J, Geng T, Cao Z, Karginov T, Hu Y, Li X, Chiari C, Qyang Y, Vella A, Fan Z, Vanaja S, Rathinam V, Witczak C, Bogan J, Wang P. UBXN9 governs GLUT4-mediated spatial confinement of RIG-I-like receptors and signaling. Nature Immunology 2024, 25: 2234-2246. PMID: 39567760, DOI: 10.1038/s41590-024-02004-7.Peer-Reviewed Original ResearchConceptsRIG-I-like receptorsRIG-I-like receptor signalingCytosolic RIG-I-like receptorsAntiviral immunityPlasma membrane tetheringRNA virus infectionGlucose transportInnate antiviral immunityCytoplasmic RIG-I-like receptorsGolgi matrixGLUT4 translocationRLR signalingViral RNACell surfaceGLUT4GLUT4 expressionGlucose uptakeInterferon responseRNAGlycolytic reprogrammingVirus infectionHuman inflammatory myopathiesGolgiSignalUbiquitinMetastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties.
Shin J, Park J, Lim J, Jeong J, Dinesh R, Maher S, Kim J, Park S, Hong J, Wysolmerski J, Choi J, Bothwell A. Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties. ELife 2024, 13 PMID: 39535280, PMCID: PMC11560131, DOI: 10.7554/elife.97279.Peer-Reviewed Original ResearchConceptsCancer cellsDickkopf-2Analysis of transcriptomeGeneration of cancer cellsPositive cancer cellsStem cell niche factorsColon cancer cellsPaneth cell differentiationHepatocyte nuclear factor 4 alphaLysozyme positive cellsChromatin accessibilityHNF4A proteinSingle-cell RNA sequencing analysisCell propertiesPaneth cell markersSequence analysisChromatin immunoprecipitationPromoter regionTranscription factorsTranscriptome analysisColon cancerColon cancer metastasisReduction of liver metastasisDownstream targetsCell differentiation
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