Featured Publications
TNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity
Fu W, Hu W, Yi Y, Hettinghouse A, Sun G, Bi Y, He W, Zhang L, Gao G, Liu J, Toyo-oka K, Xiao G, Solit D, Loke P, Liu C. TNFR2/14-3-3ε signaling complex instructs macrophage plasticity in inflammation and autoimmunity. Journal Of Clinical Investigation 2021, 131 PMID: 34185706, PMCID: PMC8363273, DOI: 10.1172/jci144016.Peer-Reviewed Original ResearchConceptsMacrophage polarizationMacrophage plasticityPI3K/Akt/mTORPathogenesis of inflammationMyeloid-specific deletionNF-κB activationAkt/mTORInflammatory arthritisAntiinflammatory pathwayImmunoregulatory roleAutoimmune diseasesProtective effectTherapeutic implicationsInflammationTNFR2 signalingAutoimmunityTNFR2TNFR2 activationReceptor complexDiseaseIntracellular regulatorsActivationMolecule 14TNFR1ArthritisFexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against inflammatory arthritis
Liu R, Chen Y, Fu W, Wang S, Cui Y, Zhao X, Lei Z, Hettinghouse A, Liu J, Wang C, Zhang C, Bi Y, Xiao G, Chen Z, Liu C. Fexofenadine inhibits TNF signaling through targeting to cytosolic phospholipase A2 and is therapeutic against inflammatory arthritis. Annals Of The Rheumatic Diseases 2019, 78: 1524. PMID: 31302596, PMCID: PMC8157820, DOI: 10.1136/annrheumdis-2019-215543.Peer-Reviewed Original ResearchConceptsAnti-TNF activityCytosolic phospholipase A2Inflammatory arthritisTNF-α transgenic miceInflammatory arthritis modelInflammatory rheumatic diseasesCollagen-induced arthritisAnti-inflammatory activityPhospholipase A2New therapeutic interventionsActivated B cellsTNF-α signalingNecrosis factor-alpha signalingDrug affinity responsive target stabilityDBA/1 miceRheumatic diseasesArthritis modelAutoimmune diseasesCellular thermal shiftSerial screeningB cellsTransgenic miceArthritisDrug AdministrationTherapeutic interventions
2023
Pathogenic mechanisms of glucocorticoid-induced osteoporosis
Chen M, Fu W, Xu H, Liu C. Pathogenic mechanisms of glucocorticoid-induced osteoporosis. Cytokine & Growth Factor Reviews 2023, 70: 54-66. PMID: 36906448, PMCID: PMC10518688, DOI: 10.1016/j.cytogfr.2023.03.002.Peer-Reviewed Original ResearchConceptsGlucocorticoid-induced osteoporosisExogenous glucocorticoidsGC excessBone cellsBone formationImpaired bone formationMultiple adverse effectsLong-term useExcessive glucocorticoidsAutoimmune diseasesBone resorptionPrescribed medicinesEnhanced osteoclastogenesisPathogenic mechanismsProcess of osteoblastogenesisGlucocorticoidsHigh dosesOsteoclast apoptosisApoptosis of osteoblastsMature osteoclastsAdverse effectsOsteoclastsDifferentiation of osteoblastsOsteoporosisOsteoclastogenesis
2022
Penfluridol targets acid sphingomyelinase to inhibit TNF signaling and is therapeutic against inflammatory autoimmune diseases
Chen Y, Liu R, Cui Y, Hettinghouse A, Fu W, Zhang L, Zhang C, Liu C. Penfluridol targets acid sphingomyelinase to inhibit TNF signaling and is therapeutic against inflammatory autoimmune diseases. Arthritis Research & Therapy 2022, 24: 27. PMID: 35045889, PMCID: PMC8767691, DOI: 10.1186/s13075-021-02713-6.Peer-Reviewed Original ResearchConceptsInflammatory autoimmune diseaseAnti-TNF activityNF-κB activationInflammatory arthritisAutoimmune diseasesAcid sphingomyelinase activityTherapeutic effectTumor necrosis factor αInhibitory effectTNFα-transgenic miceCollagen-induced arthritisSeverity of arthritisInflammatory cytokine productionM1 macrophage polarizationBone marrow-derived macrophagesNecrosis factor αNF-κB activitySphingomyelinase activitySmall molecule drug libraryRAW 264.7 macrophage cell lineMarrow-derived macrophagesAcid sphingomyelinaseDrug affinity responsive target stabilityCytokine productionChronic schizophrenia
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
2019
Progranulin promotes diabetic fracture healing in mice with type 1 diabetes
Wei J, Zhang L, Ding Y, Liu R, Guo Y, Hettinghouse A, Buza J, De La Croix J, Li X, Einhorn T, Liu C. Progranulin promotes diabetic fracture healing in mice with type 1 diabetes. Annals Of The New York Academy Of Sciences 2019, 1460: 43-56. PMID: 31423598, PMCID: PMC8138779, DOI: 10.1111/nyas.14208.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChondrogenesisDiabetes Mellitus, ExperimentalDiabetes Mellitus, Type 1Extracellular Signal-Regulated MAP KinasesFracture HealingGene DeletionHumansInflammationMiceProgranulinsProto-Oncogene Proteins c-aktReceptors, Tumor Necrosis FactorRecombinant ProteinsSignal TransductionTOR Serine-Threonine KinasesTumor Necrosis Factor-alphaConceptsDiabetic fracture healingFracture healingTumor necrosis factor receptorProinflammatory cytokine tumor necrosisType 1 diabetes mellitusAnti-inflammatory signaling pathwaysCytokine tumor necrosisType 1 diabetesNovel therapeutic intervention strategiesGrowth factor-like moleculesTherapeutic intervention strategiesNecrosis factor receptorDiabetic fractureBone fracture healingDiabetes mellitusInsulin deficiencyAutoimmune diseasesTumor necrosisTherapeutic effectBone fracturesVivo modelDiabetesFactor receptorHealingIntervention strategiesProgranulin: 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
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 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 ResearchConceptsTNF receptorAnti-inflammatory activityBinding of TNFαAutoimmune diseasesImmune cellsExtracellular domainPGRNTNFαDTT treatment