grant
Defining the molecular basis of thrombospondin-1-induced fibro-fatty diaphragm remodeling--a driver of obesity-associated respiratory dysfunction
Organization UNIVERSITY OF MICHIGAN AT ANN ARBORLocation ANN ARBOR, UNITED STATESPosted 12 Sept 2025Deadline 30 Jun 2030
NIHUS FederalResearch GrantFY20253-D3-Dimensional3DAblationAdipocytesAdipose CellAffectAnimalsBMIBMI percentileBMI z-scoreBody TissuesBody Weight decreasedBody mass indexBreathlessnessCD47CD47 AntigenCD47 GlycoproteinCD47 geneCell BodyCell Communication and SignalingCell SignalingCell-Extracellular MatrixCellsChronicCo-cultureCocultivationCocultureCoculture TechniquesComplicationCre driverCulturing, in vitro Vertebrate, PrimaryDataDeath RateDefectDepositDepositionDiaphragmDysfunctionDyspneaECMEngineeringEsbrietExercise ToleranceExertionExtracellular MatrixFDA approvedFat CellsFibrosisFunctional disorderGEM modelGEMM modelGene ExpressionGeneticGenetically Engineered MouseHistologyHumanImpairmentIn VitroIndividualInflammatory Muscle DiseasesInflammatory MyopathyInjuryIntegrin-Associated ProteinIntracellular Communication and SignalingIntramuscularIschemiaKO miceKnock-outKnock-out MiceKnockoutKnockout MiceLSKL peptideLeannessLeu-Ser-Lys-Leu peptideLinkLipocytesLung DiseasesMER6MacrophageMature LipocyteMature fat cellMeasurementMeasuresMediatingMesenchymalMiceMice MammalsMitogensModern ManMolecularMotionMurineMusMuscleMuscle DiseaseMuscle DisordersMuscle TissueMuscular DiseasesMyopathic ConditionsMyopathic Diseases and SyndromesMyopathic disease or syndromeMyopathyMyositisMφNull MouseObese MiceObesityOrganoidsPDGF-APDGF-A proteinPDGF1PDGFAPDGFA genePDGFA proteinPathogenicityPathologicPhenotypePhysiologicPhysiologicalPhysiopathologyPickwickian SyndromePirfenidonePlatelet-Derived Growth Factor A ChainPlatelet-Derived Growth Factor Alpha PolypeptidePrimary Cell CulturesProtein SecretionProteinsPublishingPulmonary DiseasesPulmonary DisorderQuetelet indexRespirationRespiration DisordersRespiratory DiaphragmRespiratory DisorderRespiratory MusclesSignal TransductionSignal Transduction SystemsSignalingSourceStructureSurface Antigen Identified by Monoclonal Antibody 1D8SystemTSP-1TSP1TestingThinnessThrombospondin 1TissuesVentilatory MusclesWeightWeight GainWeight IncreaseWeight LossWeight ReductionWhole Body Plethysmographyadipogenesisadiposityantifibrotic agentantifibrotic medicationantifibrotic therapyantifibrotic treatmentbiological signal transductionbody weight gainbody weight increasebody weight lossbreathing disordercell typeclinical relevanceclinically relevantcohortcorpulencediet controldiet-associated obesitydiet-induced obesitydiet-related obesitydietary controldisease of the lungdisorder of the lungexperimentexperimental researchexperimental studyexperimentsfeedingfibrogenesisgenetically engineered mouse modelgenetically engineered murine modelhuman subjectimprovedinhibitorinjuriesleucyl-seryl-lysyl-leucyl peptidelipid biosynthesislipogenesislung disordermortality ratemortality ratiomouse modelmurine modelmuscle degenerationmuscularmuscular disordernovelob/ob mouseobesity hypoventilation syndromeobesity preventionpathophysiologypharmacologicplatelet-derived growth factor Apre-clinicalpreclinicalprevent obesityprogenitorprogenitor cell poolprogenitor cell populationprogenitor cell proliferationprogenitor poolprogenitor populationprogenitor proliferationpulmonaryrespiratoryrespiratory dysfunctionrespiratory mechanismstem and progenitor cell populationstem and progenitor cell proliferationstem cell poolstem cell populationstem cell proliferationtargeted agenttherapeutic targetthree dimensionalultrasoundweightswt gainwt-loss
Description preview
ABSTRACT
Breathing disorders affect most individuals with obesity—and while respiratory muscle dysfunction occurs with
elevated BMI, its underlying pathophysiology and potential therapeutic targeting in obesity-associated pulmonary
compromise are largely uninvestigated. Mice subjected to diet-induced obesity (DIO), develop diaphragm
weakness. In…
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