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 ResearchMeSH Keywords14-3-3 ProteinsAnimalsArthritis, ExperimentalAutoimmunityHumansInflammationMacrophagesMiceMice, KnockoutMultiprotein ComplexesProgranulinsRAW 264.7 CellsReceptors, Tumor Necrosis Factor, Type IISignal TransductionConceptsMacrophage polarizationMacrophage plasticityPI3K/Akt/mTORPathogenesis of inflammationMyeloid-specific deletionNF-κB activationAkt/mTORInflammatory arthritisAntiinflammatory pathwayImmunoregulatory roleAutoimmune diseasesProtective effectTherapeutic implicationsInflammationTNFR2 signalingAutoimmunityTNFR2TNFR2 activationReceptor complexDiseaseIntracellular regulatorsActivationMolecule 14TNFR1Arthritis14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis
Fu W, Hettinghouse A, Chen Y, Hu W, Ding X, Chen M, Ding Y, Mundra J, Song W, Liu R, Yi Y, Attur M, Samuels J, Strauss E, Leucht P, Schwarzkopf R, Liu C. 14-3-3 epsilon is an intracellular component of TNFR2 receptor complex and its activation protects against osteoarthritis. Annals Of The Rheumatic Diseases 2021, 80: 1615-1627. PMID: 34226187, PMCID: PMC8595573, DOI: 10.1136/annrheumdis-2021-220000.Peer-Reviewed Original ResearchMeSH Keywords14-3-3 ProteinsAnimalsCartilage, ArticularChondrocytesEts-Domain Protein Elk-1HumansMiceMice, KnockoutNF-kappa BOsteoarthritisProgranulinsReceptors, Tumor Necrosis Factor, Type IISignal TransductionConceptsPathogenesis of osteoarthritisTNFR2 complexTherapeutic effectSingle-cell RNA-seqIntracellular componentsReceptor complexExtracellular signal-regulated kinaseNuclear factor kappa BSignal-regulated kinaseCommon joint diseaseFactor kappa BChondrocyte-specific deletionProteomic screenElk-1RNA-seqTranscription factorsCell-based assaysTNF signalingTNFR2 pathwayInducible componentJoint diseaseActivity screenTherapeutic targetKappa BOsteoarthritisThe 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 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 ResearchMeSH KeywordsAnabolic AgentsAnimalsBone RegenerationDiabetes Mellitus, Type 2Fracture HealingFractures, BoneHumansMiceMice, TransgenicOsteogenesisProgranulinsReceptors, Tumor Necrosis Factor, Type IITumor Necrosis Factor-alphaConceptsType 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 ResearchMeSH KeywordsCells, CulturedEnzyme-Linked Immunosorbent AssayOsteogenesisProgranulinsProtein BindingProtein Interaction MappingReceptors, Tumor Necrosis Factor, Type IIStructure-Activity RelationshipTumor Necrosis Factor-alphaConceptsAnti-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