Featured Publications
Progranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling
Zhao Y, Liu B, Tian Q, Wei J, Richbourgh B, Liu C. Progranulin protects against osteoarthritis through interacting with TNF-α and β-Catenin signalling. Annals Of The Rheumatic Diseases 2014, 74: 2244. PMID: 25169730, PMCID: PMC4408266, DOI: 10.1136/annrheumdis-2014-205779.Peer-Reviewed Original ResearchConceptsPGRN-deficient miceProgression of OAOA modelTumor necrosis factor αMechanism of progranulinRecombinant PGRN proteinArthritis mouse modelOA-like phenotypeRole of progranulinNecrosis factor αPathogenesis of OAJoint degenerative diseaseTNF receptor 2Degradation of cartilageExtracellular signal-regulated kinase 1/2Signal-regulated kinase 1/2Β-catenin signalingInflammatory actionsOA progressionAnabolic biomarkersAnabolic effectsOA developmentSafranin O stainingTherapeutic roleMouse modelADAMTS-7 forms a positive feedback loop with TNF-α in the pathogenesis of osteoarthritis
Lai Y, Bai X, Zhao Y, Tian Q, Liu B, Lin E, Chen Y, Lee B, Appleton C, Beier F, Yu X, Liu C. ADAMTS-7 forms a positive feedback loop with TNF-α in the pathogenesis of osteoarthritis. Annals Of The Rheumatic Diseases 2013, 73: 1575. PMID: 23928557, PMCID: PMC4418017, DOI: 10.1136/annrheumdis-2013-203561.Peer-Reviewed Original ResearchConceptsADAMTS-7ADAMTS-7 expressionRat OA modelPathogenesis of osteoarthritisNF-κB signalingOA modelOA progressionCartilage degradationOA-like phenotypeTumor necrosis factorProgression of osteoarthritisJoint degenerative diseaseDownstream NF-κB signalingPotential molecular targetsPositive feedback loopShort-limbed dwarfismDisease progressionOA developmentNecrosis factorSafranin O stainingYoung miceUpregulated TNFReporter gene assayOsteoarthritisTransgenic mice
2021
Progranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease
Zhao X, Liberti R, Jian J, Fu W, Hettinghouse A, Sun Y, Liu C. Progranulin associates with Rab2 and is involved in autophagosome-lysosome fusion in Gaucher disease. Journal Of Molecular Medicine 2021, 99: 1639-1654. PMID: 34453183, PMCID: PMC8541919, DOI: 10.1007/s00109-021-02127-6.Peer-Reviewed Original ResearchConceptsLysosomal storage diseaseGaucher diseaseAutophagosome-lysosome fusionCommon lysosomal storage diseasePGRN deficiencyNovel therapiesAnimal modelsProgranulinLC3-IIMolecular targetsCrucial mediatorCritical moleculesStorage diseaseDiseaseAutophagic fluxC-terminal fragmentImpaired fusionPatient fibroblastsAutophagyImpairmentKey regulator
2020
In Vitro Physical and Functional Interaction Assays to Examine the Binding of Progranulin Derivative Atsttrin to TNFR2 and Its Anti-TNFα Activity
Fu W, Hettinghouse A, Liu C. In Vitro Physical and Functional Interaction Assays to Examine the Binding of Progranulin Derivative Atsttrin to TNFR2 and Its Anti-TNFα Activity. Methods In Molecular Biology 2020, 2248: 109-119. PMID: 33185871, PMCID: PMC8112733, DOI: 10.1007/978-1-0716-1130-2_8.Peer-Reviewed Original ResearchConceptsAnti-TNFα activityAutoimmune diseasesTartrate-resistant acid phosphatase (TRAP) stainingAnti-TNFα therapyCollagen-induced arthritisInflammatory disease modelsGood therapeutic effectAcid phosphatase stainingGrowth factor-like moleculesTNF inhibitorsTherapeutic effectTNFα activityProgranulinFunctional inhibitionTNFR2AtsttrinDisease modelsPhosphatase stainingTNFRTNFαDiseaseInhibitionCritical roleDirect bindingHigh affinity
2018
p204 Is Required for Canonical Lipopolysaccharide-induced TLR4 Signaling in Mice
Yi Y, Jian J, Gonzalez-Gugel E, Shi Y, Tian Q, Fu W, Hettinghouse A, Song W, Liu R, He M, Qi H, Yang J, Du X, Xiao G, Chen L, Liu C. p204 Is Required for Canonical Lipopolysaccharide-induced TLR4 Signaling in Mice. EBioMedicine 2018, 29: 78-91. PMID: 29472103, PMCID: PMC5925582, DOI: 10.1016/j.ebiom.2018.02.012.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedCytokinesGenotypeImmunity, InnateInflammasomesInflammation MediatorsInterferon Regulatory Factor-3Interferon-betaLipopolysaccharidesMacrophage ActivationMacrophagesMiceMice, KnockoutModels, BiologicalNF-kappa BNuclear ProteinsPhosphoproteinsProtein BindingProtein MultimerizationRAW 264.7 CellsShock, SepticSignal TransductionToll-Like Receptor 4ConceptsPro-inflammatory cytokinesLPS challengeIRF-3 pathwayDimerization of TLR4Serum levelsLPS-TLR4TLR4 signalingNF-ĸBAnimal modelsPyrin domainInnate immunityExtracellular LPSInterferon-inducible p200 familyInfectious diseasesLPSMicePotential targetTLR4IFNCytokinesMacrophagesBacterial DNASignificant defectsDramatic reductionPathway
2017
Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models
Wei J, Fu W, Ding Y, Hettinghouse A, Lendhey M, Schwarzkopf R, Kennedy O, Liu C. Progranulin derivative Atsttrin protects against early osteoarthritis in mouse and rat models. Arthritis Research & Therapy 2017, 19: 280. PMID: 29258611, PMCID: PMC5735869, DOI: 10.1186/s13075-017-1485-8.Peer-Reviewed Original ResearchConceptsTherapeutic effectOA modelPain-related markersAnti-catabolic effectsRole of progranulinDegenerative joint diseaseMurine OA modelMultiple murine modelsNew therapeutic alternativesTumor necrosis factor receptorIntra-articular deliveryNecrosis factor receptorInflammatory arthritisPGRN deficiencyOA phenotypeSafranin O stainingTherapeutic alternativeRat modelJoint diseaseOsteoarthritis progressionPreventative effectMurine modelCartilage degradationDegenerative factorsEarly osteoarthritis
2016
Foxo4‐ and Stat3‐dependent IL‐10 production by progranulin in regulatory T cells restrains inflammatory arthritis
Fu W, Hu W, Shi L, Mundra J, Xiao G, Dustin M, Liu C. Foxo4‐ and Stat3‐dependent IL‐10 production by progranulin in regulatory T cells restrains inflammatory arthritis. The FASEB Journal 2016, 31: 1354-1367. PMID: 28011648, PMCID: PMC5349791, DOI: 10.1096/fj.201601134r.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, ExperimentalCell Cycle ProteinsCells, CulturedForkhead Transcription FactorsGranulinsIntercellular Signaling Peptides and ProteinsInterleukin-10MAP Kinase Signaling SystemMiceMice, Inbred DBAPhosphatidylinositol 3-KinasesProgranulinsSTAT3 Transcription FactorT-Lymphocytes, RegulatoryConceptsIL-10 productionRegulatory T cellsInflammatory arthritisIL-10T cellsAnti-inflammatory cytokine IL-10Forkhead box protein O4PI3K pathwayCollagen-induced arthritisCytokine IL-10Green fluorescent protein reporter miceTranscription factorsSequencing screenSignal transducerJNK signalingTranscription 3K pathwayImmunological mechanismsAutoimmune diseasesInflammatory conditionsMouse modelArthritisPresent new insightsReporter miceProgranulinChondro-protective effects of low intensity pulsed ultrasound
Uddin S, Richbourgh B, Ding Y, Hettinghouse A, Komatsu D, Qin Y, Liu C. Chondro-protective effects of low intensity pulsed ultrasound. Osteoarthritis And Cartilage 2016, 24: 1989-1998. PMID: 27364595, PMCID: PMC5071131, DOI: 10.1016/j.joca.2016.06.014.Peer-Reviewed Original ResearchMeSH KeywordsCartilage, ArticularCells, CulturedChondrocytesHumansInterleukin-1betaOsteoarthritisUltrasonic WavesConceptsIL-1βHuman cartilage explantsCartilage degradationMesenchymal stem cellsIL-1β induced activationPotential therapeutic effectsChondro-protective effectsPathogenesis of osteoarthritisLIPUS stimulationCartilage explantsChondrocyte migrationWestern blot analysisLoss of proteoglycanTherapeutic effectNFκB p65Catabolic actionMetabolic alterationsNFκB pathwayOsteoarthritisReduced expressionChondrocyte metabolismInduced activationMechanical stimulationLIPUSStimulation
2014
Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism
Zanin-Zhorov A, Weiss J, Nyuydzefe M, Chen W, Scher J, Mo R, Depoil D, Rao N, Liu B, Wei J, Lucas S, Koslow M, Roche M, Schueller O, Weiss S, Poyurovsky M, Tonra J, Hippen K, Dustin M, Blazar B, Liu C, Waksal S. Selective oral ROCK2 inhibitor down-regulates IL-21 and IL-17 secretion in human T cells via STAT3-dependent mechanism. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 16814-16819. PMID: 25385601, PMCID: PMC4250132, DOI: 10.1073/pnas.1414189111.Peer-Reviewed Original ResearchConceptsT cellsIL-17IL-21Forkhead box P3 (Foxp3) expressionRegulatory T cell subsetsPhase 1 clinical trialCollagen-induced arthritisIL-17 secretionRegulatory T cellsRheumatoid arthritis patientsTreatment of autoimmunityBox P3 expressionT cell subsetsDevelopment of autoimmunityROCK2 inhibitorIFN regulatory factor 4Healthy human subjectsT cell receptor stimulationIL-21 promoterSTAT3-dependent mechanismRegulatory factor 4Human T cellsArthritis patientsSiRNA-mediated inhibitionProinflammatory cytokines
2013
Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains
Jian J, Zhao S, Tian Q, Gonzalez-Gugel E, Mundra J, Uddin S, Liu B, Richbourgh B, Brunetti R, Liu C. Progranulin directly binds to the CRD2 and CRD3 of TNFR extracellular domains. FEBS Letters 2013, 587: 3428-3436. PMID: 24070898, PMCID: PMC3826980, DOI: 10.1016/j.febslet.2013.09.024.Peer-Reviewed Original ResearchThe promotion of bone healing by progranulin, a downstream molecule of BMP-2, through interacting with TNF/TNFR signaling
Zhao Y, Tian Q, Frenkel S, Liu C. The promotion of bone healing by progranulin, a downstream molecule of BMP-2, through interacting with TNF/TNFR signaling. Biomaterials 2013, 34: 6412-6421. PMID: 23746860, PMCID: PMC3713419, DOI: 10.1016/j.biomaterials.2013.05.030.Peer-Reviewed Original ResearchConceptsBone healing processBone formationHealing processEctopic bone formationTNF-α transgenic miceBone healingTNFR2-deficient miceRole of PGRNTreatment of fracturesTNF-α signalingEndochondral ossificationPotential molecular targetsEctopic bone formation modelInflammatory osteoclastogenesisTNF/TNFRPGRN deficiencyInflammatory conditionsDeficient miceRecombinant PGRNBone regenerationTransgenic micePGRNMiceCritical mediatorGrowth factor
2010
Granulin epithelin precursor: a bone morphogenic protein 2‐inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis
Feng J, Guo F, Jiang B, Zhang Y, Frenkel S, Wang D, Tang W, Xie Y, Liu C. Granulin epithelin precursor: a bone morphogenic protein 2‐inducible growth factor that activates Erk1/2 signaling and JunB transcription factor in chondrogenesis. The FASEB Journal 2010, 24: 1879-1892. PMID: 20124436, PMCID: PMC2874481, DOI: 10.1096/fj.09-144659.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersBlotting, WesternBone Morphogenetic Protein 2CartilageCell DifferentiationCells, CulturedChondrocytesChondrogenesisChromatin ImmunoprecipitationFetusGene Expression ProfilingHumansImmunoenzyme TechniquesIn Situ HybridizationIntercellular Signaling Peptides and ProteinsMesenchymal Stem CellsMiceMice, Inbred C3HMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Oligonucleotide Array Sequence AnalysisProgranulinsProto-Oncogene Proteins c-junRabbitsReverse Transcriptase Polymerase Chain ReactionRNA ProbesRNA, MessengerSignal TransductionConceptsJunB transcription factorKey downstream moleculeGranulin-epithelin precursorChondrocyte differentiationTranscription factorsDownstream moleculesNovel critical roleGrowth factorBone morphogenic proteinBone morphogenic protein-2Molecular eventsMesenchymal stem cellsERK1/2 signalingProtein 2Morphogenic proteinStem cellsDifferentiationBMP2Critical roleTissue regenerationVivoSignalingCartilage repairProteinChondrogenesis
2009
Cartilage Oligomeric Matrix Protein Maintains the Contractile Phenotype of Vascular Smooth Muscle Cells by Interacting With &agr;7&bgr;1 Integrin
Wang L, Zheng J, Du Y, Huang Y, Li J, Liu B, Liu C, Zhu Y, Gao Y, Xu Q, Kong W, Wang X. Cartilage Oligomeric Matrix Protein Maintains the Contractile Phenotype of Vascular Smooth Muscle Cells by Interacting With &agr;7&bgr;1 Integrin. Circulation Research 2009, 106: 514-525. PMID: 20019333, DOI: 10.1161/circresaha.109.202762.Peer-Reviewed Original ResearchMeSH KeywordsAdenoviridaeAnimalsAntigens, CDAorta, ThoracicBecaplerminCarotid Artery InjuriesCatheterizationCell DifferentiationCells, CulturedExtracellular MatrixExtracellular Matrix ProteinsGene Knockdown TechniquesGenetic VectorsGlycoproteinsIntegrin alpha ChainsIntegrinsMaleMatrilin ProteinsMuscle ContractionMuscle ProteinsMuscle, Smooth, VascularMyocytes, Smooth MusclePhenotypePlatelet-Derived Growth FactorProtein Interaction MappingProto-Oncogene Proteins c-sisRatsRats, Sprague-DawleyRecombinant Fusion ProteinsRNA, Small InterferingConceptsVascular smooth muscle cellsCartilage oligomeric matrix proteinEffects of COMPContractile phenotypeFocal adhesion assemblyVSMC differentiation marker genesAdenoviral overexpressionSmooth muscle cellsNormal vascular smooth muscle cellsVSMC phenotype switchingDifferentiation marker genesActin fiber organizationMuscle cellsAdhesion assemblyVascular extracellular matrixVSMC contractile phenotypeMarker genesDifferentiated stateRat vascular smooth muscle cellsPhenotype switchingPlatelet-derived growthVSMC adhesionMatrix proteinsVSMC dedifferentiationSmall interferingADAMTS-7 Mediates Vascular Smooth Muscle Cell Migration and Neointima Formation in Balloon-Injured Rat Arteries
Wang L, Zheng J, Bai X, Liu B, Liu C, Xu Q, Zhu Y, Wang N, Kong W, Wang X. ADAMTS-7 Mediates Vascular Smooth Muscle Cell Migration and Neointima Formation in Balloon-Injured Rat Arteries. Circulation Research 2009, 104: 688-698. PMID: 19168437, DOI: 10.1161/circresaha.108.188425.Peer-Reviewed Original ResearchMeSH KeywordsADAM ProteinsADAMTS7 ProteinAnimalsBecaplerminCarotid ArteriesCarotid Artery InjuriesCatheterizationCell MovementCells, CulturedDisease Models, AnimalExtracellular Matrix ProteinsGlycoproteinsHyperplasiaMaleMatrilin ProteinsMuscle, Smooth, VascularMyocytes, Smooth MuscleNF-kappa BPlatelet-Derived Growth FactorProto-Oncogene Proteins c-sisRatsRats, Sprague-DawleyRNA InterferenceRNA, Small InterferingTime FactorsTranscription Factor AP-1Transduction, GeneticTumor Necrosis Factor-alphaTunica IntimaConceptsVascular smooth muscle cellsCartilage oligomeric matrix proteinADAMTS-7VSMC migrationIntimal thickeningNeointima formationProinflammatory cytokine tumor necrosis factor alphaCytokine tumor necrosis factor alphaTumor necrosis factor alphaADAMTS-7 levelsVascular smooth muscle cell migrationDevelopment of atherosclerosisPrimary vascular smooth muscle cellsSmooth muscle cell migrationNecrosis factor alphaNovel therapeutic targetSmooth muscle cellsMuscle cell migrationPlatelet-derived growthFamily of proteinasesMigration/invasionOligomeric matrix proteinPerivascular administrationBalloon injuryVascular injury
2007
Cartilage Oligomeric Matrix Protein Associates with Granulin-Epithelin Precursor (GEP) and Potentiates GEP-stimulated Chondrocyte Proliferation*
Xu K, Zhang Y, Ilalov K, Carlson C, Feng J, Di Cesare P, Liu C. Cartilage Oligomeric Matrix Protein Associates with Granulin-Epithelin Precursor (GEP) and Potentiates GEP-stimulated Chondrocyte Proliferation*. Journal Of Biological Chemistry 2007, 282: 11347-11355. PMID: 17307734, DOI: 10.1074/jbc.m608744200.Peer-Reviewed Original ResearchConceptsGranulin-epithelin precursorCartilage oligomeric matrix proteinMutant cartilage oligomeric matrix proteinTwo-hybrid systemCo-immunoprecipitation assaysFunctional genetic screensChondrocyte proliferationHuman cartilage oligomeric matrix proteinGenetic screenRat chondrosarcoma cellsProtein associatesGrowth factorRepeat domainBiological functionsFunctional domainsMouse embryosMatrix proteinsAnti-COMP antibodiesChondrosarcoma cellsOligomeric matrix proteinAutocrine growth factorMultiple epiphyseal dysplasiaPericellular matrixPrimary human chondrocytesRepeat units