2022
Molecular determinants of peri‐apical targeting of inositol 1,4,5‐trisphosphate receptor type 3 in cholangiocytes
Rodrigues MA, Gomes DA, Fiorotto R, Guerra MT, Weerachayaphorn J, Bo T, Sessa WC, Strazzabosco M, Nathanson MH. Molecular determinants of peri‐apical targeting of inositol 1,4,5‐trisphosphate receptor type 3 in cholangiocytes. Hepatology Communications 2022, 6: 2748-2764. PMID: 35852334, PMCID: PMC9512452, DOI: 10.1002/hep4.2042.Peer-Reviewed Original ResearchConceptsLipid raftsCaveolin-1Intact lipid raftsType 3 inositol trisphosphate receptorApical regionC-terminal amino acidsTrisphosphate receptor type 3Madin-Darby canine kidney cellsCanine kidney cellsFluorescence microscopy techniquesInositol trisphosphate receptorApical localizationTrisphosphate receptorHeavy chain 9Molecular determinantsChemical disruptionAmino acidsITPR3RaftsKidney cellsIntracellular CaFinal common eventReceptor type 3Release channelMYH9
2021
Loss of endothelial glucocorticoid receptor promotes angiogenesis via upregulation of Wnt/β-catenin pathway
Liu B, Zhou H, Zhang T, Gao X, Tao B, Xing H, Zhuang Z, Dardik A, Kyriakides TR, Goodwin JE. Loss of endothelial glucocorticoid receptor promotes angiogenesis via upregulation of Wnt/β-catenin pathway. Angiogenesis 2021, 24: 631-645. PMID: 33650028, PMCID: PMC8292305, DOI: 10.1007/s10456-021-09773-x.Peer-Reviewed Original ResearchConceptsWnt/β-catenin signalingWnt/β-catenin pathwayΒ-catenin signalingΒ-catenin pathwayAutophagy fluxKey biological processesGlucocorticoid receptorNuclear receptor familyTube formation assaysEndothelial cellsBiological processesCanonical WntP62 degradationReceptor familyFormation assaysAbsence of GRCell viability assaysProcess of angiogenesisWntGR regulationSignalingVivo assaysQuantitative PCRKey receptorPathway
2017
Macrophage-Restricted Shp2 Tyrosine Phosphatase Acts as a Rheostat for MMP12 through TGF-β Activation in the Prevention of Age-Related Emphysema in Mice
Xu J, Tao B, Guo X, Zhou S, Li Y, Zhang Y, Zhou Z, Cheng H, Zhang X, Ke Y. Macrophage-Restricted Shp2 Tyrosine Phosphatase Acts as a Rheostat for MMP12 through TGF-β Activation in the Prevention of Age-Related Emphysema in Mice. The Journal Of Immunology 2017, 199: 2323-2332. PMID: 28814604, DOI: 10.4049/jimmunol.1601696.Peer-Reviewed Original ResearchConceptsMatrix metalloproteinasesActivation of alveolar macrophagesLevels of matrix metalloproteinasesElevated levels of matrix metalloproteinasesChronic lung disordersFunction of Shp2Activation of macrophagesProtein tyrosine phosphatase 2Development of emphysemaLong-term observation periodAttenuated Smad2/3 phosphorylationElevation of matrix metalloproteinasesProduction of matrix metalloproteinasesLoss of Shp2Tyrosine phosphatase 2MMP12 expressionPotential etiologiesAged miceLung disordersDestruction of alveolar wallsPulmonary emphysemaSmad2/3 phosphorylationAlveolar macrophagesAlveolar morphologyExtracellular matrix degradation
2016
Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells
Kraehling JR, Chidlow JH, Rajagopal C, Sugiyama MG, Fowler JW, Lee MY, Zhang X, Ramírez CM, Park EJ, Tao B, Chen K, Kuruvilla L, Larriveé B, Folta-Stogniew E, Ola R, Rotllan N, Zhou W, Nagle MW, Herz J, Williams KJ, Eichmann A, Lee WL, Fernández-Hernando C, Sessa WC. Genome-wide RNAi screen reveals ALK1 mediates LDL uptake and transcytosis in endothelial cells. Nature Communications 2016, 7: 13516. PMID: 27869117, PMCID: PMC5121336, DOI: 10.1038/ncomms13516.Peer-Reviewed Original ResearchConceptsActivin-like kinase 1Wide RNAi screenGWA data setsLDL uptakeEndothelial cellsIdentification of pathwaysLDL receptorRNAi screenEndocytic pathwayLysosomal degradationKinase 1LDL transcytosisPhysiological roleGenetic ablationUptake of LDLPathwayFunctional LDL receptorsCellsLow affinityTranscytosisUptakeALK1Unique opportunityAortic endotheliumAnimalsCellular Phenotypic Analysis of Macrophage Activation Unveils Kinetic Responses of Agents Targeting Phosphorylation
Cao Q, Yao J, Li H, Tao B, Cai Y, Xiao P, Cheng H, Ke Y. Cellular Phenotypic Analysis of Macrophage Activation Unveils Kinetic Responses of Agents Targeting Phosphorylation. SLAS DISCOVERY 2016, 22: 51-57. PMID: 27554457, DOI: 10.1177/1087057116663166.Peer-Reviewed Original ResearchConceptsEndpoint assayHigh-throughput mannerRegulation of macrophage activationImpedance-based assayHost immune systemCell response profilesMicrobial productsPathogen clearanceGlobal screeningPhysiologically relevant dataMacrophage functionCellular impedanceMacrophage activationAssayPreventing autoimmune diseasesImmune systemKinase/phosphatasePlastic cellsPathogensMacrophagesAutoimmune diseasesReal-timeHostReal time
2014
Myeloid-Specific Disruption of Tyrosine Phosphatase Shp2 Promotes Alternative Activation of Macrophages and Predisposes Mice to Pulmonary Fibrosis
Tao B, Jin W, Xu J, Liang Z, Yao J, Zhang Y, Wang K, Cheng H, Zhang X, Ke Y. Myeloid-Specific Disruption of Tyrosine Phosphatase Shp2 Promotes Alternative Activation of Macrophages and Predisposes Mice to Pulmonary Fibrosis. The Journal Of Immunology 2014, 193: 2801-2811. PMID: 25127857, DOI: 10.4049/jimmunol.1303463.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsArginaseBleomycinBronchoalveolar Lavage FluidCells, CulturedChitinInflammationInterleukin-13Interleukin-4Interleukin-5Janus Kinase 1LungMacrophage ActivationMacrophages, AlveolarMiceMice, KnockoutProtein Tyrosine Phosphatase, Non-Receptor Type 11Pulmonary FibrosisReceptors, Cell SurfaceRNA InterferenceRNA, Small InterferingSchistosoma japonicumSchistosomiasis japonicaSignal TransductionSTAT6 Transcription FactorConceptsPulmonary fibrosisIL-4RAM2 polarizationAlternative activation of macrophagesBleomycin-induced inflammationActivation of M2 macrophagesM2 polarization in vitroActivation of macrophagesPolarization in vitroTyrosine phosphatase SHP2Association of Jak1Loss of Shp2Enhanced M2 polarizationM2 macrophagesMacrophage skewingAlveolar macrophagesCre recombinaseFibrosisPhosphatase SHP2M2 phenotypeM2 skewingMacrophagesSHP2Predisposed mice
2012
Docking protein Gab2 regulates mucin expression and goblet cell hyperplasia through TYK2/STAT6 pathway
Zhang X, Zhang Y, Tao B, Wang D, Cheng H, Wang K, Zhou R, Xie Q, Ke Y. Docking protein Gab2 regulates mucin expression and goblet cell hyperplasia through TYK2/STAT6 pathway. The FASEB Journal 2012, 26: 4603-4613. PMID: 22859374, DOI: 10.1096/fj.12-211755.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAnimalsEpithelial CellsGene Expression RegulationGoblet CellsHumansHyperplasiaHypersensitivityInterleukin-13LungLung NeoplasmsMiceMice, KnockoutMucinsMucusOvalbuminPhosphoproteinsPulmonary Disease, Chronic ObstructiveRespiratory MucosaSTAT6 Transcription FactorTYK2 KinaseConceptsGoblet cell hyperplasiaChronic obstructive pulmonary diseaseExpression of mucin genesKnockdown of Gab2Mucin gene expressionGab2 knockoutIn vivo roleCell hyperplasiaGab2Lung cancerRegulate growthMucin genesMolecular basisGene expressionPulmonary diseaseChronic pulmonary diseaseAirway inflammatory diseasesAnalysis of lungPotential involvementObstructive pulmonary diseaseAirway epitheliaMucin expressionAllergy modelCystic fibrosisInflammatory diseasesLoss of Shp2 in alveoli epithelia induces deregulated surfactant homeostasis, resulting in spontaneous pulmonary fibrosis
Zhang X, Zhang Y, Tao B, Teng L, Li Y, Cao R, Gui Q, Ye M, Mou X, Cheng H, Hu H, Zhou R, Wu X, Xie Q, Ning W, Lai M, Shen H, Feng G, Ke Y. Loss of Shp2 in alveoli epithelia induces deregulated surfactant homeostasis, resulting in spontaneous pulmonary fibrosis. The FASEB Journal 2012, 26: 2338-2350. PMID: 22362894, DOI: 10.1096/fj.11-200139.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP-Binding Cassette TransportersFibroblast Growth FactorsHomeostasisMiceMice, KnockoutNuclear ProteinsProtein Tyrosine Phosphatase, Non-Receptor Type 11Pulmonary AlveoliPulmonary FibrosisPulmonary Surfactant-Associated ProteinsPulmonary SurfactantsThyroid Nuclear Factor 1Transcription FactorsConceptsATP-binding cassette subfamily A member 3Thyroid transcription factor-1Spontaneous pulmonary fibrosisPulmonary fibrosisSurfactant homeostasisTyrosine phosphatase SHP2Expression of thyroid transcription factor-1Surfactant proteinsAlveolar epithelial apoptosisInterstitial pulmonary fibrosisPhosphatase SHP2Investigate in vivo functionsTranscription factor 1Lung branching morphogenesisEpithelial apoptosisPulmonary surfactant proteinsAlveolar epitheliaLung injuryIneffective repairLoss of Shp2Minimal inflammationAT-IIEpithelial budsAlveolar functionFibrosis
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