2025
ATP-gated P2x7 receptors express at type II auditory nerves and required for efferent hearing control and noise protection
Liang C, Zhai T, Chen J, Fang S, Zhu Y, Liu L, Yu N, Zhao H. ATP-gated P2x7 receptors express at type II auditory nerves and required for efferent hearing control and noise protection. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2421995122. PMID: 40540593, PMCID: PMC12207453, DOI: 10.1073/pnas.2421995122.Peer-Reviewed Original ResearchConceptsCochlear efferent systemHearing sensitivityATP-gated P2X7 receptorP2X7 receptorOuter hair cellsAuditory nerveInnervate outer hair cellsEfferent systemAuditory brainstem responseSpiral ganglion (SGActive cochlear amplificationActive cochlear mechanicsEfferent nervesP2X7 KO miceIncreased susceptibility to noiseSusceptibility to noiseNeuronal functionAcoustic startle responseHair cellsBrainstem responseHearing lossEfferent suppressionHearing disordersOHC electromotilityNoise exposureEndothelial CLEC5A drives barrier dysfunction and vascular leakage responsible for lung injury in bacterial pneumonia and sepsis
Zhang T, Huang X, Goodwin J, Wen R, Liu Y, Yang Y, Zhang T, Zheng Y, Chen A, Hao P, Tong X, Yang N, Liu C. Endothelial CLEC5A drives barrier dysfunction and vascular leakage responsible for lung injury in bacterial pneumonia and sepsis. Science Advances 2025, 11: eadt7589. PMID: 40498836, PMCID: PMC12154197, DOI: 10.1126/sciadv.adt7589.Peer-Reviewed Original ResearchConceptsVascular leakagePuncture (CLP)-induced polymicrobial sepsisRegulating endothelial barrier functionCLP-challenged miceEndothelial barrier dysfunctionTrans-endothelial electrical resistanceEndothelial barrier functionLipopolysaccharide (LPS)-induced endotoxemiaVascular endothelial cellsPattern recognition receptorsSurvival benefitMultiorgan failurePolymicrobial sepsisTrans-endothelial migrationCecal ligationBacterial pneumoniaLung injuryBarrier dysfunctionVascular injurySingle-cell RNA sequencingDecreased mortalityInflammatory stormBacterial infectionsHeterogeneity of vascular endothelial cellsSepsisLKB1 regulates ILC3 postnatal development and effector function through metabolic programming
Zhang H, Zhao L, Zhang Q, Hu L, Su X, Sun J, Shen L. LKB1 regulates ILC3 postnatal development and effector function through metabolic programming. Frontiers In Immunology 2025, 16: 1587256. PMID: 40539052, PMCID: PMC12176730, DOI: 10.3389/fimmu.2025.1587256.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein Kinase KinasesAMP-Activated Protein KinasesAnimalsCitrobacter rodentiumEnterobacteriaceae InfectionsImmunity, InnateInterleukin-22InterleukinsIntestinal MucosaIntestinesLymphocytesMetabolic ReprogrammingMiceMice, Inbred C57BLMice, KnockoutProtein Serine-Threonine KinasesConceptsLiver kinase B1Intestinal immune homeostasisEffector functionsPostnatal developmentImmune homeostasisFlow cytometryGroup 3 innate lymphoid cellsMetabolic regulationIntestinal immunityLKB1 deficiencyIL-22 productionLKB1-deficient miceConditional knockout miceIntestinal inflammatory responsePotential therapeutic implicationsImpaired cell metabolismILC3 numbersIntestinal ILC3sLymphoid cellsILC3 functionCytokine productionILC3sKnockout miceMitochondrial massILC3 activationIL‐6 signaling regulates the inflammatory response without impacting pathogen burden during influenza‐associated pulmonary aspergillosis
Sharma L, Singh R, Tolman N, Ngeow C, Duray A, Naghshtabrizi N, Ahmad A, Bain W, Robinson K. IL‐6 signaling regulates the inflammatory response without impacting pathogen burden during influenza‐associated pulmonary aspergillosis. Physiological Reports 2025, 13: e70372. PMID: 40420617, PMCID: PMC12106949, DOI: 10.14814/phy2.70372.Peer-Reviewed Original ResearchConceptsAF infectionAspergillus fumigatusInterleukin-6IL-6 signalingLung inflammationInfluenza-associated pulmonary aspergillosisInterleukin-6 knockout miceNeutrophilic lung inflammationBronchoalveolar lavage fluidEpithelial cell damageLung capillary permeabilitySusceptibility to opportunistic pathogensPulmonary aspergillosisClinical courseLavage fluidKnockout miceOpportunistic pathogenRAGE levelsEpithelial integrityMouse modelIL-6Pathological inflammationTissue injuryInflammatory responseViral infectionGly-βMCA modulates bile acid metabolism to reduce hepatobiliary injury in Mdr2 KO mice
Hasan M, Wang H, Luo W, Du Y, Li T. Gly-βMCA modulates bile acid metabolism to reduce hepatobiliary injury in Mdr2 KO mice. AJP Gastrointestinal And Liver Physiology 2025, 329: g45-g57. PMID: 40418643, PMCID: PMC12178242, DOI: 10.1152/ajpgi.00044.2025.Peer-Reviewed Original ResearchConceptsKO miceBile acid compositionBile acid pool sizeBile acid poolBile acid hydrophobicityHepatic bile acidsHepatobiliary toxicityBile acid metabolismMale miceTherapeutic benefitCholestasis modelMdr2-KO miceDecreased liver injuryBile acidsSerum alkaline phosphataseBile acid absorptionAlkaline phosphataseFecal bile acid excretionAcid compositionDiminished therapeutic efficacyImpaired bile flowAcid metabolismHepatobiliary injuryUnique pharmacokineticsBiliary injuryChanges in the FXR-cistrome and alterations in bile acid physiology in Wilson disease
Wooton-Kee C, Yalamanchili H, Mohamed I, Hassan M, Setchell K, Rivas M, Coskun A, Putluri V, Putluri N, Jalal P, Schilsky M, Moore D. Changes in the FXR-cistrome and alterations in bile acid physiology in Wilson disease. Hepatology Communications 2025, 9: e0707. PMID: 40408300, PMCID: PMC12106221, DOI: 10.1097/hc9.0000000000000707.Peer-Reviewed Original ResearchConceptsWild-type miceFarnesoid X receptorWilson's diseaseNon-parenchymal cellsDistal intergenic regionsLiver bile acid concentrationWD patientsHealthy controlsMetabolic target genesFarnesoid X Receptor RegulationBile salt export pumpIntergenic regionFXR activationAutosomal recessive disorderBile acid homeostasisBile acid physiologyFarnesoid X receptor activationPromoter regionHomeostasis pathwaysBile acid metabolismDecreasing FXR activityTarget genesBile acid profilesMarker genesStress pathwaysSecretory leukocyte protease inhibitor influences periarticular joint inflammation in Borrelia burgdorferi-infected mice
Yu Q, Tang X, Hart T, Homer R, Belperron A, Bockenstedt L, Ring A, Nakamura A, Fikrig E. Secretory leukocyte protease inhibitor influences periarticular joint inflammation in Borrelia burgdorferi-infected mice. ELife 2025, 14: rp104913. PMID: 40392222, PMCID: PMC12092001, DOI: 10.7554/elife.104913.Peer-Reviewed Original ResearchConceptsSecretory leukocyte protease inhibitorJoint inflammationC57BL/6 miceHigher infection loadTick-borne infectionsWild-type control miceClinical manifestations of infectionDevelopment of Lyme arthritisElevated serum levelsExcessive pro-inflammatory responsesManifestations of infectionProtease inhibitorsPro-inflammatory responseAnkle joint tissueInfection loadPromote tissue repairAnti-inflammatory effectsSerum levelsPeriarticular swellingClinical manifestationsControl miceTibiotarsal jointMMP-8Lyme diseaseIL-6GALNT14 deficiency: connecting multiple links in the IgA nephropathy pathogenetic chain
Pell J, Menon M. GALNT14 deficiency: connecting multiple links in the IgA nephropathy pathogenetic chain. Journal Of Clinical Investigation 2025, 135: e192687. PMID: 40371648, PMCID: PMC12077885, DOI: 10.1172/jci192687.Peer-Reviewed Original ResearchSARM1 loss protects retinal ganglion cells in a mouse model of Autosomal Dominant Optic Atrophy
Ding C, Ndiaye P, Campbell S, Fry M, Gong J, Wienbar S, Gibbs W, Morquette P, Chao L, H. M, Schwarz T. SARM1 loss protects retinal ganglion cells in a mouse model of Autosomal Dominant Optic Atrophy. Journal Of Clinical Investigation 2025, 135: e191315. PMID: 40344041, PMCID: PMC12165793, DOI: 10.1172/jci191315.Peer-Reviewed Original ResearchConceptsAutosomal dominant optic atrophyRetinal ganglion cellsOptic atrophy type 1Dominant optic atrophyOptic atrophyMouse modelRGC degenerationGanglion cellsOptic nerve degenerationHereditary optic neuropathyMitochondrial intermembrane spaceRGC lossOptic neuropathyRGC functionVision lossNerve degenerationIntermembrane spaceType 1Mitochondrial fragmentationDegeneration phenotypeMitochondrial defectsTherapeutic targetMembrane dynamicsMiceTIR motifEndoplasmic reticulum Nogo drives AgRP neuronal activation and feeding behavior
Jin S, Yoon N, Wei M, Worgall T, Rubinelli L, Horvath T, Min W, Diano N, di Lorenzo A, Diano S. Endoplasmic reticulum Nogo drives AgRP neuronal activation and feeding behavior. Cell Metabolism 2025, 37: 1400-1412.e8. PMID: 40334659, PMCID: PMC12136989, DOI: 10.1016/j.cmet.2025.04.005.Peer-Reviewed Original ResearchConceptsAgRP neuron activityNogo-AAgRP neuronsNeuronal activityCeramide levelsNogo-A expressionCellular lipid metabolismIntracellular lipid transportSphingolipid de novo biosynthesisDownregulation of enzymesIncreased ceramide levelsLipid metabolismHigh-fat diet-induced obesityFeeding behaviorAgouti-related proteinControl of feedingControlling lipid metabolismAssociated with brain developmentWhole-body metabolismFatty acid oxidationReticulon 4Food intakeMitochondrial functionSynaptic plasticityLipid transportCardiomyocyte-specific NHE1 overexpression confers protection against myocardial infarction during hyperglycemia
Jiang K, Su F, Deng R, Xu Y, Qin A, Yuan X, Xing D, Chen Y, Wang D, Shen L, Hwa J, Hou L, Xiang Y. Cardiomyocyte-specific NHE1 overexpression confers protection against myocardial infarction during hyperglycemia. Cardiovascular Diabetology 2025, 24: 184. PMID: 40287728, PMCID: PMC12034198, DOI: 10.1186/s12933-025-02743-3.Peer-Reviewed Original ResearchConceptsNa+/H+ exchanger 1Na+/H+ exchanger 1 activationAcute hyperglycemiaMyocardial infarctionNHE1 overexpressionNHE1 activityTherapeutic strategiesCardiomyocyte necroptosisHistory of diabetes mellitusReduced extracellular Na+Worsened cardiac dysfunctionRetrospective cohort studyDouble knockout miceIschemia-reperfusion modelNon-diabetic individualsPost-MI patientsReduced infarct sizePathophysiology of MIBackgroundAcute hyperglycemiaElevated BNPMLKL knockoutReduced cardiomyocyte deathAcute myocardial infarctionExtracellular Na+Intracellular Na+Gene-dose effect of the glutathione biosynthesis gene on ascorbate deficiency in mice
Strand R, Orlicky D, Chen Y. Gene-dose effect of the glutathione biosynthesis gene on ascorbate deficiency in mice. Biochemical And Biophysical Research Communications 2025, 766: 151900. PMID: 40294460, PMCID: PMC12058385, DOI: 10.1016/j.bbrc.2025.151900.Peer-Reviewed Original ResearchConceptsGene-dose effectAscorbate deficiencyTissue GSH levelsDouble-knockoutVitamin CDietary vitamin CAllele dosage effectGlutamate-cysteine ligaseMiceClinical interplayGSH levelsOxidative stressBrain tissueRedox imbalanceGCLMDosage effectBrain functionDeficiencyGlutathione biosynthesis genesIncreased vulnerabilityBrainPhenotypic outcomesModifier subunitRedox balanceGSH biosynthesisMyeloperoxidase impacts vascular function by altering perivascular adipocytes’ secretome and phenotype in obesity
Hof A, Landerer M, Peitsmeyer P, Herzog R, Alber J, Ahdab M, Nettersheim F, Mehrkens D, Geißen S, Braumann S, Guthoff H, von Stein P, Nemade H, Picard F, Braun R, Hoyer F, Brüning J, Pfeifer A, Hildebrand S, Winkels H, Baldus S, Adam M, Schäkel J, Mollenhauer M. Myeloperoxidase impacts vascular function by altering perivascular adipocytes’ secretome and phenotype in obesity. Cell Reports Medicine 2025, 6: 102087. PMID: 40252642, PMCID: PMC12147848, DOI: 10.1016/j.xcrm.2025.102087.Peer-Reviewed Original ResearchConceptsPerivascular adipose tissueVascular functionEndothelial functionObesity-related cardiovascular diseaseImmune cell frequenciesAdipose tissuePerivascular adipose tissue inflammationReduced arterial stiffnessInflammatory cytokine releaseHuman white adipocytesInfluence vascular functionObese patientsAdipocyte marker expressionMyeloid cellsCardiovascular morbidityImmune cellsCytokine releaseEndothelial dysfunctionIncreased inflammationAdipocyte secretomeCell frequencyMarker expressionMPO levelsConsumption in vivoNitrotyrosine formationSustained tenascin-C expression drives neointimal hyperplasia and promotes aortocaval fistula failure
Gonzalez L, Zhang W, Bai H, Taniguchi R, Ramachandra A, Jovin D, Ohashi Y, Nguyen M, Thaxton C, Yatsula B, Vazquez-Padron R, Humphrey J, Martin K, Kyriakides T, Dardik A. Sustained tenascin-C expression drives neointimal hyperplasia and promotes aortocaval fistula failure. AJP Heart And Circulatory Physiology 2025, 328: h1147-h1167. PMID: 40247455, PMCID: PMC12150301, DOI: 10.1152/ajpheart.00661.2024.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArteriovenous Shunt, SurgicalDisease Models, AnimalGraft Occlusion, VascularHuman Umbilical Vein Endothelial CellsHumansHyperplasiaMacrophagesMaleMiceMice, Inbred C57BLMice, KnockoutMyocytes, Smooth MuscleNeointimaNF-kappa BTenascinThrombomodulinVascular PatencyVascular RemodelingVena Cava, InferiorConceptsArteriovenous fistula patencyTenascin-C expressionArteriovenous fistulaTissue factor expressionEnd-stage kidney diseaseAnti-inflammatory macrophage polarizationNeointimal hyperplasiaWT miceTenascin-CInflammatory microenvironmentWild-typeFactor expressionMacrophage polarizationArteriovenous fistula outcomesArteriovenous fistula failurePatent arteriovenous fistulaVein smooth muscle cellsArteriovenous fistula maturationSmooth muscle cellsOccluded arteriovenous fistulaHuman umbilical vein smooth muscle cellsImprove dialysis outcomesHuman umbilical vein endothelial cellsRegulation of inflammationNF-kB activationMitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism
Steiner K, Young A, Patterson A, Sugiura A, Watson M, Preston S, Zhelonkin A, Jennings E, Chi C, Heintzman D, Pahnke A, Toudji Y, Hatem Z, Madden M, Arner E, Sewell A, Blount A, Okparaugo R, Fallman E, Krystofiak E, Sheldon R, Gibson-Corley K, Voss K, Nowinski S, Jones R, Mogilenko D, Rathmell J. Mitochondrial fatty acid synthesis and MECR regulate CD4+ T cell function and oxidative metabolism. The Journal Of Immunology 2025, 214: 958-976. PMID: 40204636, PMCID: PMC12123211, DOI: 10.1093/jimmun/vkaf034.Peer-Reviewed Original ResearchConceptsT cell subsetsCD4+ T cell subsetsMitochondrial fatty acid synthesisT cell functionT cellsFatty acid synthesisDecreased mitochondrial respirationTricarboxylic acid intermediatesLipid metabolism genesT cell fateSensitivity to ferroptosisIncreased cell deathCD4+ T cell functionCD8+ T cell numbersCD4+ T cell proliferationMitochondrial stressMetabolic genesCD4+ T cellsCRISPR/Cas9 screenMitochondrial respirationModel of inflammatory bowel diseaseAcid synthesisFitness disadvantageMemory T cellsT cell numbersSrsf3-Dependent APA Drives Macrophage Maturation and Limits Atherosclerosis
Yang X, Zhang X, Tian Y, Yang J, Jia Y, Xie Y, Cheng L, Chen S, Wu L, Qin Y, Zhao Z, Zhao D, Wei Y. Srsf3-Dependent APA Drives Macrophage Maturation and Limits Atherosclerosis. Circulation Research 2025, 136: 985-1009. PMID: 40160097, DOI: 10.1161/circresaha.124.326111.Peer-Reviewed Original ResearchConceptsAlternative polyadenylationAssociated with atherosclerosis progressionUntranslated regionRNA sequencingExpression of chemokinesRegulation of cell fateAlternative polyadenylation patternsEfficient mitochondrial translationMetabolic labeling assaysSingle-cell RNA sequencingIntegrated stress responseMyeloid deletionLow-density lipoproteinMonocytes to macrophagesImpairment of protein synthesisPhagocytic impairmentMetabolomic profilesMacrophage maturationPrecursor nicotinamide mononucleotideCirculating monocytesIntegrated stress response inhibitorLesional cellsHistopathological analysisProatherosclerotic effectsNicotinamide mononucleotide treatmentLoss of GalNAc-T14 links O-glycosylation defects to alterations in B cell homing in IgA nephropathy
Prakash S, Steers N, Li Y, Sanchez-Rodriguez E, Verbitsky M, Robbins I, Simpson J, Pathak S, Raska M, Reily C, Ng A, Liang J, DeMaria N, Katiraei A, O'Stevens K, Fischman C, Shapiro S, Kodali S, McCutchan J, Park H, Eliby D, Delsante M, Allegri L, Fiaccadori E, Bodria M, Marasa M, Raveche E, Julian B, Uhlemann A, Kiryluk K, Zhang H, D'Agati V, Sanna-Cherchi S, Novak J, Gharavi A. Loss of GalNAc-T14 links O-glycosylation defects to alterations in B cell homing in IgA nephropathy. Journal Of Clinical Investigation 2025, 135: e181164. PMID: 40153534, PMCID: PMC12077892, DOI: 10.1172/jci181164.Peer-Reviewed Original ResearchConceptsO-glycosylationAberrant O-glycosylationIgA nephropathyMucosal immunityN-acetylgalactosaminyltransferaseElevated serum IgA levelsAdoptive-transfer experimentsB-cell homingSerum IgA levelsProtein O-glycosylationIgA-producing cellsGlomerular IgA depositionImmune-complex formationPathogenesis of IgANIgA1 hinge regionIgA1-producing cellsPeripheral bloodImpaired homingKidney injuryB cellsB lymphocytesIgA levelsLoF variantsIgA depositionGalNAc-T14MAP 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, PMCID: PMC11889166, 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 strokeChemokines
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