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 linePathology
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 regulator
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 activityIn 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
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 ResearchConceptsGD patientsHealthy controlsGaucher diseaseDownstream moleculesExpression of CHI3L1Serum CHI3L1Serum levelsPGRN levelsTherapeutic effectClinical biomarkersPatientsPotential biomarkersNull miceCHI3L1ProgranulinElevated levelsBiomarkersWhole-genome microarraysDiseaseCHIT1Genome microarraysNovel regulatorImmunohistochemistryLevelsMice
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 miceProgranulin