Featured Publications
PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases
Zhao X, Lin Y, Liou B, Fu W, Jian J, Fannin V, Zhang W, Setchell K, Grabowski G, Sun Y, Liu C. PGRN deficiency exacerbates, whereas a brain penetrant PGRN derivative protects, GBA1 mutation-associated pathologies and diseases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 120: e2210442120. PMID: 36574647, PMCID: PMC9910439, DOI: 10.1073/pnas.2210442120.Peer-Reviewed Original ResearchConceptsBlood-brain barrierParkinson's diseaseGaucher diseasePGRN deficiencyPD-like phenotypesRelevant mouse modelRare lysosomal storage diseaseCommon neurodegenerative disorderVisceral symptomsNeurobehavioral deficitsSevere neuroinflammationPD pathologyLysosomal storage diseaseTherapeutic studiesMouse modelNeuronopathic involvementProgranulinImpaired autophagyNeurodegenerative disordersGD phenotypeEarly onsetMiceDiseaseFirst linePathologyThe 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 signalingAtsttrinTNFR
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 regulatorProgranulin promotes bone fracture healing via TNFR pathways in mice with type 2 diabetes mellitus
Ding Y, Wei J, Hettinghouse A, Li G, Li X, Einhorn T, Liu C. Progranulin promotes bone fracture healing via TNFR pathways in mice with type 2 diabetes mellitus. Annals Of The New York Academy Of Sciences 2021, 1490: 77-89. PMID: 33543485, PMCID: PMC8138780, DOI: 10.1111/nyas.14568.Peer-Reviewed Original ResearchConceptsType 2 diabetes mellitusRole of progranulinBone fracture healingFracture healingDiabetes mellitusT2DM modelType 1 diabetic conditionAnti-inflammatory activityTranscription-polymerase chain reactionLocal administrationBone marrow cellsExogenous progranulinMKR micePGRN effectsPrimary bone marrow cellsFracture riskDiabetic conditionsPGRN mRNABone fragilityImmunohistochemical stainingMetabolic disordersRecombinant progranulinBone fracturesProgranulinTherapeutic potential
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 affinityMonitoring Atsttrin-Mediated Inhibition of TNFα/NF-κβ Activation Through In Vivo Bioluminescence Imaging
Hettinghouse A, Fu W, Liu C. Monitoring Atsttrin-Mediated Inhibition of TNFα/NF-κβ Activation Through In Vivo Bioluminescence Imaging. Methods In Molecular Biology 2020, 2248: 201-210. PMID: 33185877, PMCID: PMC8140391, DOI: 10.1007/978-1-0716-1130-2_14.Peer-Reviewed Original ResearchConceptsTumor necrosis factorDouble mutant miceNF-κBOverexpression of TNFMutant miceBioluminescence imagingTransgenic reporter mouse modelNF-κB luciferaseNF-κβ activationVivo bioluminescence imagingReporter mouse modelAutoimmune conditionsTNF-TgNF-κβNecrosis factorImmune responseMouse modelMolecular mediatorsTransgenic modelTherapeutic objectivesVivo efficacyProgranulinPotential therapeuticsAtsttrinLuciferase activity
2019
Progranulin: A conductor of receptors orchestra, a chaperone of lysosomal enzymes and a therapeutic target for multiple diseases
Cui Y, Hettinghouse A, Liu C. Progranulin: A conductor of receptors orchestra, a chaperone of lysosomal enzymes and a therapeutic target for multiple diseases. Cytokine & Growth Factor Reviews 2019, 45: 53-64. PMID: 30733059, PMCID: PMC6450552, DOI: 10.1016/j.cytogfr.2019.01.002.Peer-Reviewed Original ResearchConceptsTherapeutic targetInflammatory autoimmune diseaseRare lysosomal storage diseaseCommon neurological diseasesPromising therapeutic targetPreclinical disease modelsDrug development strategiesExtracellular progranulinAutoimmune diseasesClinical trialsLysosomal storage diseaseTherapeutic strategiesNeurological diseasesKinds of diseasesProgranulinDiseaseDisease modelsStorage diseaseMultiple membrane receptorsPathological statesTissue repairMultiple diseasesLysosomal enzymesPleiotropic functionsDiverse pathological states
2018
Establishment of a Modified Collagen-Induced Arthritis Mouse Model to Investigate the Anti-inflammatory Activity of Progranulin in Inflammatory Arthritis
Wei J, Liu C. Establishment of a Modified Collagen-Induced Arthritis Mouse Model to Investigate the Anti-inflammatory Activity of Progranulin in Inflammatory Arthritis. Methods In Molecular Biology 2018, 1806: 305-313. PMID: 29956284, DOI: 10.1007/978-1-4939-8559-3_20.Peer-Reviewed Original ResearchConceptsChicken type II collagenArthritis mouse modelPGRN-deficient miceInflammatory arthritisAnti-inflammatory activityMouse modelDeficient miceCollagen-Induced Arthritis Mouse ModelProtective roleCollagen-induced arthritis (CIA) mouse modelAutoimmune inflammatory arthritisHuman rheumatoid arthritisAutoimmune modelComplete Freund'sRheumatoid arthritisDegenerative arthritisPathological featuresDegenerative osteoarthritisControl littermatesCIA modelArthritisHigh incidenceType II collagenProgranulinDisease modelsChitinase-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 ResearchConceptsGD patientsHealthy controlsGaucher diseaseDownstream moleculesExpression of CHI3L1Serum CHI3L1Serum levelsPGRN levelsTherapeutic effectClinical biomarkersPatientsPotential biomarkersNull miceCHI3L1ProgranulinElevated levelsBiomarkersWhole-genome microarraysDiseaseCHIT1Genome microarraysNovel regulatorImmunohistochemistryLevelsMice
2017
Progranulin acts as a shared chaperone and regulates multiple lysosomal enzymes
Jian J, Hettinghouse A, Liu C. Progranulin acts as a shared chaperone and regulates multiple lysosomal enzymes. Genes & Diseases 2017, 4: 125-126. PMID: 28944282, PMCID: PMC5609500, DOI: 10.1016/j.gendis.2017.05.001.Peer-Reviewed Original ResearchMultiple lysosomal enzymesLysosomal enzymesE domainLysosomal enzyme cathepsin DLysosomal storage diseaseLysosomal enzyme β-glucocerebrosidaseEnzyme cathepsin DC-terminusChaperonesMolecular mechanismsChaperone moleculesEnzyme β-glucocerebrosidaseNeuronal ceroid lipofuscinosisStorage diseaseGaucher diseaseNull miceEnzymeCeroid lipofuscinosisCathepsin DGene variantsMutationsΒ-glucocerebrosidaseRole of progranulinImportant roleProgranulin
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 miceProgranulinProgranulin 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
2013
Progranulin 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 ResearchConceptsInflammatory skin diseaseSeverity of dermatitisMouse dermatitis modelNF-κB signalingPotential molecular targetsInflammatory arthritisDermatitis modelSkin inflammationPGRN levelsSevere inflammationProgranulin deficiencySkin diseasesProtective roleInflammationMolecular targetsPGRNAtsttrinDermatitisOxazoloneArthritisTNFαProgranulinDiseaseMiceProtein
2011
Progranulin: 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 ResearchConceptsGrowth 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 ResearchConceptsTNF 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 proteinsInflammationCytokinesScience Signaling Podcast: 26 April 2011
Liu C, VanHook A. Science Signaling Podcast: 26 April 2011. Science Signaling 2011, 4 DOI: 10.1126/scisignal.2002099.Peer-Reviewed Original ResearchTumor necrosis factor receptorInflammatory arthritisSevere inflammatory arthritisTumor necrosis factorSeverity of symptomsGrowth factor progranulinNecrosis factor receptorPGRN treatmentRheumatoid arthritisNecrosis factorNormal miceMouse modelArthritisGrowth factorSenior authorProgranulinFactor receptorSymptomsMiceGroup findingsImmunizationTNFαFindingsSeverity