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 ResearchMeSH KeywordsAnimalsBeta CateninCartilage, ArticularCells, CulturedDisease Models, AnimalHumansIntercellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLOsteoarthritisProgranulinsProtein PrecursorsSignal TransductionTumor Necrosis Factor-alphaConceptsPGRN-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 modelThe Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice
Tang W, Lu Y, Tian QY, Zhang Y, Guo FJ, Liu GY, Syed NM, Lai Y, Lin EA, Kong L, Su J, Yin F, Ding AH, Zanin-Zhorov A, Dustin ML, Tao J, Craft J, Yin Z, Feng JQ, Abramson SB, Yu XP, Liu CJ. The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice. Science 2011, 332: 478-484. PMID: 21393509, PMCID: PMC3104397, DOI: 10.1126/science.1199214.Peer-Reviewed Original ResearchMeSH KeywordsAdolescentAdultAgedAnimalsAnti-Inflammatory Agents, Non-SteroidalArthritis, ExperimentalCartilage, ArticularFemaleGranulinsHumansIntercellular Signaling Peptides and ProteinsLigandsMaleMiceMice, Inbred StrainsMice, KnockoutMice, TransgenicMiddle AgedProgranulinsProtein Interaction Domains and MotifsReceptors, Tumor Necrosis Factor, Type IReceptors, Tumor Necrosis Factor, Type IIRecombinant Fusion ProteinsRecombinant ProteinsSignal TransductionT-Lymphocytes, RegulatoryTumor Necrosis Factor-alphaYoung AdultConceptsInflammatory arthritisAdministration of progranulinAntagonist of TNFαCollagen-induced arthritisArthritis mouse modelPGRN-deficient miceNew potential therapeutic interventionsPotential therapeutic interventionsGrowth factor progranulinNecrosis factor receptorRheumatoid arthritisMouse modelArthritisTherapeutic interventionsProgranulinTNF receptorFactor receptorMiceReceptorsInflammationTissue repairTNFαIntracellular signalingAtsttrinTNFRProgranulin Recruits HSP70 to β-Glucocerebrosidase and Is Therapeutic Against Gaucher Disease
Jian J, Tian Q, Hettinghouse A, Zhao S, Liu H, Wei J, Grunig G, Zhang W, Setchell K, Sun Y, Overkleeft H, Chan G, Liu C. Progranulin Recruits HSP70 to β-Glucocerebrosidase and Is Therapeutic Against Gaucher Disease. EBioMedicine 2016, 13: 212-224. PMID: 27789271, PMCID: PMC5264254, DOI: 10.1016/j.ebiom.2016.10.010.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineDisease Models, AnimalFibroblastsGaucher DiseaseGlucosylceramidaseHSP70 Heat-Shock ProteinsHumansIntercellular Signaling Peptides and ProteinsLysosome-Associated Membrane GlycoproteinsLysosomesMiceMice, KnockoutPhenotypeProgranulinsProtein AggregatesProtein BindingRecombinant ProteinsStress, PhysiologicalConceptsGaucher diseaseLysosomal storage diseaseStorage diseaseCommon lysosomal storage diseaseNew therapeutic interventionsΒ-glucocerebrosidaseProgranulin insufficiencyAnimal modelsTherapeutic interventionsDiseasePGRNDisease phenotypePatient fibroblastsGCaseComplex-associated proteinsLysosomal localizationHSP70DeficiencyAssociation Between Progranulin and Gaucher Disease
Jian J, Zhao S, Tian QY, Liu H, Zhao Y, Chen WC, Grunig G, Torres PA, Wang BC, Zeng B, Pastores G, Tang W, Sun Y, Grabowski GA, Kong MX, Wang G, Chen Y, Liang F, Overkleeft HS, Saunders-Pullman R, Chan GL, Liu CJ. Association Between Progranulin and Gaucher Disease. EBioMedicine 2016, 11: 127-137. PMID: 27515686, PMCID: PMC5049935, DOI: 10.1016/j.ebiom.2016.08.004.Peer-Reviewed Original ResearchMeSH KeywordsAdultAgedAllelesAnimalsCase-Control StudiesDisease Models, AnimalEnzyme ActivationFemaleGaucher DiseaseGene FrequencyGenetic Association StudiesGenotypeHumansIntercellular Signaling Peptides and ProteinsLysosomesMaleMiceMice, KnockoutMiddle AgedMutationPhenotypePolymorphism, Single NucleotideProgranulinsProtein TransportConceptsGD patientsHealthy controlsGaucher diseaseGRN genePGRN KO miceSerum PGRN levelsPGRN-deficient miceHealthy control samplesSerum levelsPGRN levelsGaucher-like cellsKO miceTherapeutic effectRecombinant PGRNGeneral populationPatientsAnimal modelsBone marrowGBA1 geneLysosomal localizationProgranulin geneNull micePGRNDiseaseMice
2019
A novel mechanism of EAE resistance highlights the conflicting roles of progranulin-mediated immunosuppression and antigen processing
Hettinghouse A, Gao G, Liu C. A novel mechanism of EAE resistance highlights the conflicting roles of progranulin-mediated immunosuppression and antigen processing. Cellular & Molecular Immunology 2019, 18: 506-507. PMID: 31511641, PMCID: PMC8026965, DOI: 10.1038/s41423-019-0292-3.Peer-Reviewed Original ResearchAntigen PresentationImmune ToleranceImmunosuppression TherapyIntercellular Signaling Peptides and ProteinsProgranulins
2018
Chitinase-3-like Protein 1: A Progranulin Downstream Molecule and Potential Biomarker for Gaucher Disease
Jian J, Chen Y, Liberti R, Fu W, Hu W, Saunders-Pullman R, Pastores G, Chen Y, Sun Y, Grabowski G, Liu C. Chitinase-3-like Protein 1: A Progranulin Downstream Molecule and Potential Biomarker for Gaucher Disease. EBioMedicine 2018, 28: 251-260. PMID: 29396296, PMCID: PMC5835567, DOI: 10.1016/j.ebiom.2018.01.022.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiomarkersChitinase-3-Like Protein 1ChitinasesDisease Models, AnimalGaucher DiseaseGranulinsHumansIntercellular Signaling Peptides and ProteinsMice, Inbred C57BLMice, KnockoutPhenotypeProgranulinsUp-RegulationConceptsGD patientsHealthy controlsGaucher diseaseDownstream moleculesExpression of CHI3L1Serum CHI3L1Serum levelsPGRN levelsTherapeutic effectClinical biomarkersPatientsPotential biomarkersNull miceCHI3L1ProgranulinElevated levelsBiomarkersWhole-genome microarraysDiseaseCHIT1Genome microarraysNovel regulatorImmunohistochemistryLevelsMice
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 ResearchMeSH KeywordsAnimalsCartilage, ArticularCells, CulturedChondrocytesDisease Models, AnimalGranulinsHumansIntercellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutOsteoarthritisProgranulinsRatsRats, Sprague-DawleyRecombinant Fusion ProteinsConceptsTherapeutic 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 miceProgranulinReview: Novel Insights Into Tumor Necrosis Factor Receptor, Death Receptor 3, and Progranulin Pathways in Arthritis and Bone Remodeling
Williams A, Wang E, Thurner L, Liu C. Review: Novel Insights Into Tumor Necrosis Factor Receptor, Death Receptor 3, and Progranulin Pathways in Arthritis and Bone Remodeling. Arthritis & Rheumatology 2016, 68: 2845-2856. PMID: 27428882, PMCID: PMC5599977, DOI: 10.1002/art.39816.Peer-Reviewed Original ResearchArthritisBone RemodelingHumansIntercellular Signaling Peptides and ProteinsProgranulinsReceptors, Tumor Necrosis FactorReceptors, Tumor Necrosis Factor, Member 25Signal TransductionExtracellular matrix protein 1, a direct targeting molecule of parathyroid hormone‐related peptide, negatively regulates chondrogenesis and endochondral ossification via associating with progranulin growth factor
Kong L, Zhao Y, Tian Q, Feng J, Kobayashi T, Merregaert J, Liu C. Extracellular matrix protein 1, a direct targeting molecule of parathyroid hormone‐related peptide, negatively regulates chondrogenesis and endochondral ossification via associating with progranulin growth factor. The FASEB Journal 2016, 30: 2741-2754. PMID: 27075243, PMCID: PMC4970607, DOI: 10.1096/fj.201600261r.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChondrogenesisExtracellular Matrix ProteinsGene Expression Regulation, DevelopmentalGranulinsIntercellular Signaling Peptides and ProteinsMice, TransgenicOsteogenesisParathyroid Hormone-Related ProteinProgranulinsConceptsExtracellular matrix protein 1Matrix protein 1Protein 1Endochondral ossificationCellular signaling pathwaysGrowth factorRegulation of chondrogenesisEndochondral bone formationUnrecognized regulatorChondrogenic growth factorsInteraction networksPTHrP regulationCartilage developmentSignaling pathwaysParathyroid hormone-related peptideTarget transgeneMatrix proteinsChondrocyte differentiationCellular interactionsHormone-related peptideChondrogenesisChondrocyte hypertrophyPTHrP actionOverexpressionPathwayProgranulin inhibits expression and release of chemokines CXCL9 and CXCL10 in a TNFR1 dependent manner
Mundra J, Jian J, Bhagat P, Liu C. Progranulin inhibits expression and release of chemokines CXCL9 and CXCL10 in a TNFR1 dependent manner. Scientific Reports 2016, 6: 21115. PMID: 26892362, PMCID: PMC4759551, DOI: 10.1038/srep21115.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCD4-Positive T-LymphocytesChemokine CXCL10Chemokine CXCL9Cluster AnalysisDermatitis, ContactGene Expression ProfilingGene Expression RegulationIntercellular Signaling Peptides and ProteinsMacrophagesMiceMice, KnockoutProgranulinsReceptors, Tumor Necrosis Factor, Type IRecombinant ProteinsConceptsWild-type B6 micePGRN KO miceRecombinant PGRN proteinTNFR1-dependent mannerSeverity of inflammationInflammatory bowel diseaseAnti-inflammatory functionalityCXCL9 expressionTreg populationGene array analysisBowel diseaseDermatitis modelRheumatoid arthritisChemokine expressionChemokines CXCL9Autoimmune diseasesB6 micePGRN functionCXCL10 expressionKO miceT cellsPleiotrophic growth factorsImmune systemProgranulinNull mice
2014
Progranulin inhibition of TNFα
Uddin S, Mundra J, Jian J, Tian Q, Gonzalez‐Gugel E, Richbourgh B, Liu C. Progranulin inhibition of TNFα. Immunology And Cell Biology 2014, 92: 299-300. PMID: 24518982, DOI: 10.1038/icb.2014.7.Peer-Reviewed Original ResearchAnimalsHumansIntercellular Signaling Peptides and ProteinsLymphotoxin-alphaReceptors, Tumor Necrosis Factor, Type ISignal TransductionTumor Necrosis Factor-alpha
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 ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportAnimalsBinding SitesCell Line, TumorCells, CulturedCysteineHumansIntercellular Signaling Peptides and ProteinsJurkat CellsMiceProgranulinsReceptors, Tumor Necrosis FactorTumor Necrosis Factor-alphaThe 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 factorProgranulin deficiency exaggerates, whereas progranulin‐derived Atsttrin attenuates, severity of dermatitis in mice
Zhao Y, Tian Q, Liu C. Progranulin deficiency exaggerates, whereas progranulin‐derived Atsttrin attenuates, severity of dermatitis in mice. FEBS Letters 2013, 587: 1805-1810. PMID: 23669357, PMCID: PMC3683372, DOI: 10.1016/j.febslet.2013.04.037.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDermatitis, ContactGranulinsIntercellular Signaling Peptides and ProteinsMiceNF-kappa BOxazoloneProgranulinsRecombinant Fusion ProteinsSignal TransductionSkinUp-RegulationConceptsInflammatory skin diseaseSeverity of dermatitisMouse dermatitis modelNF-κB signalingPotential molecular targetsInflammatory arthritisDermatitis modelSkin inflammationPGRN levelsSevere inflammationProgranulin deficiencySkin diseasesProtective roleInflammationMolecular targetsPGRNAtsttrinDermatitisOxazoloneArthritisTNFαProgranulinDiseaseMiceProtein
2011
GEP constitutes a negative feedback loop with MyoD and acts as a novel mediator in controlling skeletal muscle differentiation
Wang D, Bai X, Tian Q, Lai Y, Lin E, Shi Y, Mu X, Feng J, Carlson C, Liu C. GEP constitutes a negative feedback loop with MyoD and acts as a novel mediator in controlling skeletal muscle differentiation. Cellular And Molecular Life Sciences 2011, 69: 1855-1873. PMID: 22179841, PMCID: PMC3319484, DOI: 10.1007/s00018-011-0901-5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBinding SitesCell DifferentiationCell LineFeedback, PhysiologicalGranulinsHEK293 CellsHumansIntercellular Signaling Peptides and ProteinsMiceMolecular Sequence DataMuscle Fibers, SkeletalMuscle, SkeletalMyoblasts, SkeletalMyoD ProteinProgranulinsConceptsMyoD transcription factorGranulin-epithelin precursorTranscription factorsMyoblast fusionMyotube formationMuscle-specific transcription factorsC2C12 myoblast fusionE-box sequenceSkeletal muscle differentiationFusion of myoblastsNegative feedback loopGrowth factorEmbryonic developmentRegulatory regionsMuscle differentiationSkeletal muscle tissueC2C12 myoblastsRegulatory loopSiRNA approachNovel mediatorAutocrine growth factorJunBKnockdown miceMyoblastsTissue repairProgranulin: A growth factor, a novel TNFR ligand and a drug target
Liu C, Bosch X. Progranulin: A growth factor, a novel TNFR ligand and a drug target. Pharmacology & Therapeutics 2011, 133: 124-132. PMID: 22008260, PMCID: PMC4429904, DOI: 10.1016/j.pharmthera.2011.10.003.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, ExperimentalAutoimmune DiseasesHumansIntercellular Signaling Peptides and ProteinsLigandsNeoplasmsNeurodegenerative DiseasesProgranulinsReceptors, Tumor Necrosis FactorConceptsGrowth factorAdministration of progranulinCollagen-induced arthritisAnti-inflammatory effectsArthritis mouse modelAnti-inflammatory propertiesExact molecular pathwaysInflammatory arthritisRheumatoid arthritisNeurotrophic factorArthritic processImmune cellsNecrosis factorMouse modelTNFR ligandsProgranulinFrontotemporal dementiaPGRN proteinArthritisPGRN geneExperimental modelCancer cellsCrucial mediatorEpithelial cellsChondrogenic growth factorsProgranulin: A promising therapeutic target for rheumatoid arthritis
Liu C. Progranulin: A promising therapeutic target for rheumatoid arthritis. FEBS Letters 2011, 585: 3675-3680. PMID: 21550343, PMCID: PMC3162080, DOI: 10.1016/j.febslet.2011.04.065.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, RheumatoidExtracellular Matrix ProteinsHumansIntercellular Signaling Peptides and ProteinsMolecular Targeted TherapyProteolysisRecombinant Fusion ProteinsConceptsTNF receptorRheumatoid arthritisAntagonist of TNFαInflammatory arthritis modelPathogenesis of arthritisPromising therapeutic targetAutocrine growth factorNew therapeutic interventionsInflammatory arthritisArthritis modelInflammatory cytokinesArthritisTherapeutic targetTherapeutic interventionsProgranulinCell surface receptorsGrowth factorExtracellular matrix proteinsSurface receptorsReceptorsAtsttrinProteolytic enzymesMatrix proteinsInflammationCytokines
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
ADAMTS-7, a Direct Target of PTHrP, Adversely Regulates Endochondral Bone Growth by Associating with and Inactivating GEP Growth Factor
Bai X, Wang D, Kong L, Zhang Y, Luan Y, Kobayashi T, Kronenberg H, Yu X, Liu C. ADAMTS-7, a Direct Target of PTHrP, Adversely Regulates Endochondral Bone Growth by Associating with and Inactivating GEP Growth Factor. Molecular And Cellular Biology 2009, 29: 4201-4219. PMID: 19487464, PMCID: PMC2715794, DOI: 10.1128/mcb.00056-09.Peer-Reviewed Original ResearchMeSH KeywordsADAM ProteinsADAMTS7 ProteinAnimalsBlotting, WesternBone and BonesBone DevelopmentCell DifferentiationCell LineCell Line, TumorChondrocytesGene Expression ProfilingHumansImmunohistochemistryImmunoprecipitationIntercellular Signaling Peptides and ProteinsMiceMice, KnockoutParathyroid Hormone-Related ProteinProgranulinsProtein BindingProtein PrecursorsReverse Transcriptase Polymerase Chain ReactionTissue Culture TechniquesTwo-Hybrid System TechniquesConceptsADAMTS-7Granulin-epithelin precursorEndochondral bone formationEndochondral bone growthGrowth factorBone formationChondrocyte differentiationBone growthDirect targetAutocrine growth factorGrowth plate chondrocytesProteolytic activityPTHrPChondrogenic growth factorsChondrocyte hypertrophyExtracellular matrix proteinsCartilage extracellular matrix proteinsImportant targetADAMTS familyInhibitionSkeletal developmentMatrix proteinsExpression patternsExtracellular matrixArthritis