2024
Novel peptide inhibitor of human tumor necrosis factor-α has antiarthritic activity
Sahu D, Gupta C, Yennamalli R, Sharma S, Roy S, Hasan S, Gupta P, Sharma V, Kashyap S, Kumar S, Dwivedi V, Zhao X, Panda A, Das H, Liu C. Novel peptide inhibitor of human tumor necrosis factor-α has antiarthritic activity. Scientific Reports 2024, 14: 12935. PMID: 38839973, PMCID: PMC11153517, DOI: 10.1038/s41598-024-63790-6.Peer-Reviewed Original ResearchConceptsProtein-protein interactionsGel mobility-shift assaysCollagen-induced arthritisMobility-shift assaysCell surface receptorsFluorescence-activated cell sortingSequence strandsBinding of TNFIn silico methodsCell deathMouse modelSurface receptorsNuclear translocationTrimer formationCell culture assaysRheumatoid arthritisVicious cycle of inflammationModel of collagen-induced arthritisTumor necrosis factor-aCell sortingMouse model of collagen-induced arthritisA549 cellsCycle of inflammationInflammatory bone destructionCulture assay
2023
Tau deficiency inhibits classically activated macrophage polarization and protects against collagen-induced arthritis in mice
Chen M, Fu W, Xu H, Liu C. Tau deficiency inhibits classically activated macrophage polarization and protects against collagen-induced arthritis in mice. Arthritis Research & Therapy 2023, 25: 146. PMID: 37559125, PMCID: PMC10410869, DOI: 10.1186/s13075-023-03133-4.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArthritis, ExperimentalArthritis, RheumatoidCytokinesMacrophagesMiceTau ProteinsConceptsInflammatory cell infiltrationPro-inflammatory cytokinesRheumatoid arthritisAnkle jointSerum levelsCell infiltrationMacrophage polarizationOsteoclast activityCartilage damagePathogenesis of RACollagen-induced arthritis modelTau-/- miceCollagen-induced arthritisInflammatory joint diseasePro-inflammatory functionsProgression of CIAPotential therapeutic targetRole of tauInflammatory arthritisBone erosionArthritis incidenceBone lossClinical scoresArthritis modelInflammatory disorders
2022
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 linePathologyInjectable recombinant block polymer gel for sustained delivery of therapeutic protein in post traumatic osteoarthritis
Katyal P, Hettinghouse A, Meleties M, Hasan S, Chen C, Cui M, Sun G, Menon R, Lin B, Regatte R, Montclare J, Liu C. Injectable recombinant block polymer gel for sustained delivery of therapeutic protein in post traumatic osteoarthritis. Biomaterials 2022, 281: 121370. PMID: 35032910, PMCID: PMC9055922, DOI: 10.1016/j.biomaterials.2022.121370.Peer-Reviewed Original ResearchConceptsUnique stimuli-responsive propertiesProtein block polymersC gelStimuli-responsive propertiesProtein-based gelsSustained deliveryProtein-based biomaterialsBlock polymersPolymer gelsNetworked gelsProlonged releaseSynthetic materialsGelTherapeutic applicationsInjectable biomaterialsExcellent candidatePhysiological temperatureTherapeutic proteinsModular natureBiomaterialsBiomechanical environmentPolymersProspective therapeuticsRabbit anterior cruciate ligament transection (ACLT) modelPenfluridol 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
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 regulatorTNFR2/14-3-3ε 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 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 ResearchConceptsPathogenesis 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 BOsteoarthritisProgranulin 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
Monitoring 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 deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice
Wang C, Zhang L, Ndong J, Hettinghouse A, Sun G, Chen C, Zhang C, Liu R, Liu C. Progranulin deficiency exacerbates spinal cord injury by promoting neuroinflammation and cell apoptosis in mice. Journal Of Neuroinflammation 2019, 16: 238. PMID: 31775776, PMCID: PMC6882111, DOI: 10.1186/s12974-019-1630-1.Peer-Reviewed Original ResearchConceptsBasso Mouse ScaleNeurological recoverySpinal cord injuryCord injuryWestern blottingWild-type littermate miceMacrophages/microgliaPromising therapeutic approachWeight-drop techniqueNew therapeutic targetsHuge economic burdenPro-apoptotic effectsPLGA thermosensitive hydrogelFunctional recoveryPGRN deficiencyPGRN expressionLittermate miceIntrathecal spaceProgranulin deficiencyTherapeutic approachesTherapeutic targetEconomic burdenWT controlsDay 21Day 7Progranulin 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 strategiesFexofenadine 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 interventionsProgranulin: 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
Progranulin associates with hexosaminidase A and ameliorates GM2 ganglioside accumulation and lysosomal storage in Tay-Sachs disease
Chen Y, Jian J, Hettinghouse A, Zhao X, Setchell K, Sun Y, Liu C. Progranulin associates with hexosaminidase A and ameliorates GM2 ganglioside accumulation and lysosomal storage in Tay-Sachs disease. Journal Of Molecular Medicine 2018, 96: 1359-1373. PMID: 30341570, PMCID: PMC6240367, DOI: 10.1007/s00109-018-1703-0.Peer-Reviewed Original ResearchRole of ADAMTS‐12 in Protecting Against Inflammatory Arthritis in Mice By Interacting With and Inactivating Proinflammatory Connective Tissue Growth Factor
Wei J, Fu W, Hettinghouse A, He W, Lipson K, Liu C. Role of ADAMTS‐12 in Protecting Against Inflammatory Arthritis in Mice By Interacting With and Inactivating Proinflammatory Connective Tissue Growth Factor. Arthritis & Rheumatology 2018, 70: 1745-1756. PMID: 29750395, PMCID: PMC6203634, DOI: 10.1002/art.40552.Peer-Reviewed Original ResearchConceptsConnective tissue growth factorCIA mouse modelADAMTS-12Inflammatory arthritisTissue growth factorMouse modelCollagen-induced arthritis modelGrowth factorRheumatoid arthritis developmentEnzyme-linked immunosorbentRA patientsArthritis developmentPannus formationSerum levelsCartilage destructionArthritis modelInflammatory cytokinesEnhanced osteoclastogenesisHealthy subjectsArthritisAnkle jointTomography scanningInflammationSusceptibility genesCritical regulatorTargeting tumor necrosis factor receptors in ankylosing spondylitis
Lata M, Hettinghouse A, Liu C. Targeting tumor necrosis factor receptors in ankylosing spondylitis. Annals Of The New York Academy Of Sciences 2018, 1442: 5-16. PMID: 30008173, PMCID: PMC6333510, DOI: 10.1111/nyas.13933.Peer-Reviewed Original ResearchConceptsRole of TNFTumor necrosis factor inhibitorsCourse of ASTargeted biologic therapiesAnti-TNF therapyAutoimmune inflammatory disorderNecrosis factor inhibitorsMore effective treatment strategiesSerious adverse effectsMultiple clinical trialsEffective treatment strategiesPathogenesis of ASTumor necrosis factor receptorNecrosis factor receptorBiologic therapyTNF inhibitorsFactor inhibitorsInflammatory disordersPathogenic roleClinical trialsTreatment strategiesImmune pathwaysTNFTNF biologyTherapyEstablishment 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 modelsMolecular regulations and therapeutic targets of Gaucher disease
Chen Y, Sud N, Hettinghouse A, Liu C. Molecular regulations and therapeutic targets of Gaucher disease. Cytokine & Growth Factor Reviews 2018, 41: 65-74. PMID: 29699937, PMCID: PMC8108120, DOI: 10.1016/j.cytogfr.2018.04.003.Peer-Reviewed Original ResearchConceptsGaucher diseaseHeat shock proteinsProper foldingMolecular regulationActivity of GCaseLysosomal localizationShock proteinsCommon lysosomal storage diseaseLysosomal appearanceIon channelsCalcium ion channelsLysosomal accumulationSaposin CLysosomal storage diseaseSubstrate glucosylceramideInflammatory mediatorsProinflammatory moleculesNew targetsPathogenic mechanismsTherapeutic targetGCaseNovel moleculesSmall moleculesDiseaseStorage diseasep204 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