2014
NLRP6 Inflammasome Orchestrates the Colonic Host-Microbial Interface by Regulating Goblet Cell Mucus Secretion
Wlodarska M, Thaiss CA, Nowarski R, Henao-Mejia J, Zhang JP, Brown EM, Frankel G, Levy M, Katz MN, Philbrick WM, Elinav E, Finlay BB, Flavell RA. NLRP6 Inflammasome Orchestrates the Colonic Host-Microbial Interface by Regulating Goblet Cell Mucus Secretion. Cell 2014, 156: 1045-1059. PMID: 24581500, PMCID: PMC4017640, DOI: 10.1016/j.cell.2014.01.026.Peer-Reviewed Original ResearchConceptsRegulatory pathwaysGoblet cell mucus secretionHost-microbial mutualismHost-microbial interfaceNLRP6 inflammasomeMucus secretionGoblet cellsBiogeographical distributionProkaryotic cellsInnate immune playersNLRP6 deficiencyGranule exocytosisImmune regulatory pathwaysInflammasome-deficient miceColonic microbiota compositionLarge intestinal lumenCritical orchestratorsImmune playersPersistent infectionMucus productionCellsIntestinal lumenPathwayMucosal surfacesMicrobiota composition
2013
Enhanced Fasting Glucose Turnover in Mice with Disrupted Action of TUG Protein in Skeletal Muscle*
Löffler MG, Birkenfeld AL, Philbrick KM, Belman JP, Habtemichael EN, Booth CJ, Castorena CM, Choi CS, Jornayvaz FR, Gassaway BM, Lee HY, Cartee GD, Philbrick W, Shulman GI, Samuel VT, Bogan JS. Enhanced Fasting Glucose Turnover in Mice with Disrupted Action of TUG Protein in Skeletal Muscle*. Journal Of Biological Chemistry 2013, 288: 20135-20150. PMID: 23744065, PMCID: PMC3711282, DOI: 10.1074/jbc.m113.458075.Peer-Reviewed Original ResearchMeSH Keywords3T3-L1 CellsAdaptor Proteins, Signal TransducingAnimalsBlood GlucoseCarbon DioxideCarrier ProteinsDeoxyglucoseFastingFemaleGlucoseGlucose Transporter Type 4GlycogenGolgi Matrix ProteinsHypoglycemic AgentsImmunoblottingInsulinIntracellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLMice, Inbred StrainsMice, TransgenicMuscle, SkeletalOxygen ConsumptionProtein TransportProteolysisConceptsGLUT4 translocationGLUT4 glucose transportersMuscle-specific transgenic expressionTransgenic miceT-tubule fractionTUG ProteinInsulin signalSystemic glucose homeostasisDiet-induced insulin resistanceHigh-fat diet-induced insulin resistanceEndoproteolytic cleavageTransgenic expressionTransgenic muscleGlucose transporterCell surfaceEnergy metabolismProteolysisTranslocationGLUT4Skeletal muscleGlucose uptakeHyperinsulinemic clamp studiesExpressionMetabolic rateTurnover
2001
Insulin secretion and IP levels in two distant lineages of the genus Mus: comparisons with rat islets
Zawalich W, Zawalich K, Tesz G, Sterpka J, Philbrick W. Insulin secretion and IP levels in two distant lineages of the genus Mus: comparisons with rat islets. AJP Endocrinology And Metabolism 2001, 280: e720-e728. PMID: 11287354, DOI: 10.1152/ajpendo.2001.280.5.e720.Peer-Reviewed Original Research
2000
βiv Spectrin, a New Spectrin Localized at Axon Initial Segments and Nodes of Ranvier in the Central and Peripheral Nervous System
Berghs S, Aggujaro D, Dirkx R, Maksimova E, Stabach P, Hermel J, Zhang J, Philbrick W, Slepnev V, Ort T, Solimena M. βiv Spectrin, a New Spectrin Localized at Axon Initial Segments and Nodes of Ranvier in the Central and Peripheral Nervous System. Journal Of Cell Biology 2000, 151: 985-1002. PMID: 11086001, PMCID: PMC2174349, DOI: 10.1083/jcb.151.5.985.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnkyrinsAutoantigensAxonsBlood ProteinsBrain ChemistryChromosomesCloning, MolecularCOS CellsCytoplasmCytoskeletonDiabetic NeuropathiesGene ExpressionHippocampusHumansIslets of LangerhansMaleMembrane ProteinsMiceMolecular Sequence DataNerve Tissue ProteinsPhosphoproteinsProtein Structure, TertiaryProtein Tyrosine PhosphatasesRanvier's NodesRatsRats, Sprague-DawleyReceptor-Like Protein Tyrosine Phosphatases, Class 8RNA, MessengerSciatic NerveSignal TransductionSodium ChannelsSpectrinConceptsPleckstrin homology domainHomology domainBetaIV spectrinActin-binding domainAxon initial segmentPutative SH3Alternative splicingSpectrin geneSpectrin repeatsDetergent extractabilityCell adhesion moleculeNodes of RanvierSubcellular fractionationTerminal halfAdditional isoformsDistinct isoformsLong isoformNorthern blotSpectrinAbundant expressionΒIV-spectrinIsoformsSpectrin antibodiesEmbryonic day 19Initial segmentParathyroid hormone-related protein induces spontaneous osteoclast formation via a paracrine cascade
Nakchbandi I, Weir E, Insogna K, Philbrick W, Broadus A. Parathyroid hormone-related protein induces spontaneous osteoclast formation via a paracrine cascade. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 7296-7300. PMID: 10829073, PMCID: PMC16539, DOI: 10.1073/pnas.110553397.Peer-Reviewed Original ResearchConceptsNumber of osteoclastsEffects of PTHrPOsteoclast formationDF cellsBone resorptionFactor expressionOsteoclastic bone resorptionDental follicle cellsHormone-related proteinOsteoclast differentiation factorStellate reticulum cellsOsteoclastogenesis inhibitory factorCoronal tooth surfacesSpontaneous osteoclast formationParacrine cascadeParathyroid hormoneEruption pathwayReticulum cellsPeripheral skeletonTooth eruptionOsteoclast precursorsPTH/PTHrP.Inhibitory factorFunctional osteoclastsCrypt cellsHepatocyte Growth Factor Overexpression in the Islet of Transgenic Mice Increases Beta Cell Proliferation, Enhances Islet Mass, and Induces Mild Hypoglycemia*
Garcia-Ocaña A, Takane K, Syed M, Philbrick W, Vasavada R, Stewart A. Hepatocyte Growth Factor Overexpression in the Islet of Transgenic Mice Increases Beta Cell Proliferation, Enhances Islet Mass, and Induces Mild Hypoglycemia*. Journal Of Biological Chemistry 2000, 275: 1226-1232. PMID: 10625667, DOI: 10.1074/jbc.275.2.1226.Peer-Reviewed Original ResearchConceptsHepatocyte growth factorRat insulin II promoterBeta-cell proliferationDiabetogenic effectMild hypoglycemiaIslet massInsulin contentOverexpression of HGFIslet numberInsulin productionBeta-cell replication rateRole of HGFHepatocyte growth factor overexpressionProliferation of isletsBeta-cell massCell proliferationGrowth factor overexpressionMesenchyme-derived cellsPancreatic areaCell replication ratesFasting statesNormal littermatesTransgenic miceHGF mRNAIslet cells
1999
Regulation of parathyroid hormone-related protein gene expression in murine keratinocytes by E1A isoforms: a role for basal promoter and Ets-1 site
Foley J, Wysolmerski J, Missero C, King C, Philbrick W. Regulation of parathyroid hormone-related protein gene expression in murine keratinocytes by E1A isoforms: a role for basal promoter and Ets-1 site. Molecular And Cellular Endocrinology 1999, 156: 13-23. PMID: 10612419, DOI: 10.1016/s0303-7207(99)00151-3.Peer-Reviewed Original ResearchMeSH KeywordsAdenovirus E1A ProteinsAnimalsBase SequenceBinding SitesCell Line, TransformedEnhancer Elements, GeneticGene Expression RegulationGenes, rasGenes, ReporterKeratinocytesLuciferasesMiceParathyroid HormoneParathyroid Hormone-Related ProteinPromoter Regions, GeneticProtein IsoformsProteinsProto-Oncogene Protein c-ets-1Proto-Oncogene ProteinsProto-Oncogene Proteins c-etsRNA, MessengerTranscription FactorsTranscription, GeneticConceptsGene expressionBasal promoterReporter constructsEts-1 siteMinimal promoter regionProtein gene expressionTransient transfection assaysReporter gene activityRepressor domainE1A oncoproteinGene activityRas transformationE1A isoformsMurine keratinocyte lineSite upstreamReporter geneTransfection assaysPromoter regionParathyroid hormone-related protein gene expression
1998
PTHrP Regulates Epidermal Differentiation in Adult Mice
Foley J, Wysolmerski J, Dreyer B, Broadus A, Philbrick W, Longely B. PTHrP Regulates Epidermal Differentiation in Adult Mice. Journal Of Investigative Dermatology 1998, 111: 1122-1128. PMID: 9856827, DOI: 10.1046/j.1523-1747.1998.00428.x.Peer-Reviewed Original ResearchConceptsPTHrP-knockout miceKeratin 14 promoterAdult miceSebaceous glandsHuman keratin 14 promoterParathyroid hormone-related peptideHyperplastic sebaceous glandsHormone-related peptideAbsence of PTHrPNumber of organsWk of agePremature acquisitionEpidermal proliferation rateMarked acanthosisTransgenic replacementReciprocal findingsTransgenic micePTHrPPTHrP geneMiceMammary glandBasal keratinocytesDisplay abnormalitiesLethal chondrodystrophyFibrotic dermisParathyroid hormone-related protein is required for tooth eruption
Philbrick W, Dreyer B, Nakchbandi I, Karaplis A. Parathyroid hormone-related protein is required for tooth eruption. Proceedings Of The National Academy Of Sciences Of The United States Of America 1998, 95: 11846-11851. PMID: 9751753, PMCID: PMC21728, DOI: 10.1073/pnas.95.20.11846.Peer-Reviewed Original ResearchConceptsPTHrP-knockout miceTooth eruptionEruption pathwayPTHrP expressionType I PTH/PTHrP receptorEnamel epitheliumPTH/PTHrP receptorOverexpression of PTHrPHormone-related proteinMonths of ageNormal tooth developmentParathyroid hormoneBone resorptionPTHrP receptorPTHrP mRNAKnockout miceTransgenic miceAlveolar boneDental mesenchymeLevel of expressionMiceBone formationSkeletal abnormalitiesTooth developmentKeratin 14Parathyroid hormone‐related protein is a developmental regulatory molecule
Philbrick W. Parathyroid hormone‐related protein is a developmental regulatory molecule. European Journal Of Oral Sciences 1998, 106: 32-37. PMID: 9541200, DOI: 10.1111/j.1600-0722.1998.tb02150.x.Peer-Reviewed Original ResearchConceptsDevelopmental regulatory moleculeOverexpression of PTHrPHormone-related proteinHormone-related peptideSingle G protein-coupled receptorG protein-coupled receptorsProtein-coupled receptorsPTHrP overexpressionHumoral hypercalcemiaTumor productsPTHrP functionsKnockout miceMammary epithelial cellsTransgenic miceRegulatory moleculesMiceEpithelial cellsPTH geneRegulatory effectsPTHrPN-terminal productType IMultiple tissuesConvincing evidenceOverexpression
1997
Bcl-2 Lies Downstream of Parathyroid Hormone–related Peptide in a Signaling Pathway That Regulates Chondrocyte Maturation during Skeletal Development
Amling M, Neff L, Tanaka S, Inoue D, Kuida K, Weir E, Philbrick W, Broadus A, Baron R. Bcl-2 Lies Downstream of Parathyroid Hormone–related Peptide in a Signaling Pathway That Regulates Chondrocyte Maturation during Skeletal Development. Journal Of Cell Biology 1997, 136: 205-213. PMID: 9008714, PMCID: PMC2132464, DOI: 10.1083/jcb.136.1.205.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsApoptosisBcl-2-Associated X ProteinBone DevelopmentCartilageCells, CulturedCollagenGene ExpressionGrowth PlateHumansHypertrophyMiceMice, KnockoutMice, TransgenicOrgan SpecificityParathyroid Hormone-Related ProteinPromoter Regions, GeneticProteinsProto-Oncogene ProteinsProto-Oncogene Proteins c-bcl-2Recombinant Fusion ProteinsSignal TransductionConceptsSkeletal developmentChondrocyte maturationBcl-2Cell deathCollagen II promoterApoptotic cell deathMutant PTH/PTHrP receptorsDevelopmental programMolecular mechanismsSignaling pathwaysCell typesGrowth plate chondrocytesTargeted disruptionGenesMetaphyseal chondrodysplasiaMaturationPTHrP geneTransgenic micePathwayPTH/PTHrP receptorAccelerated maturationSkeletal dysplasiaHormone-related peptideMajor roleChondrocytes
1996
Targeted overexpression of parathyroid hormone-related peptide in chondrocytes causes chondrodysplasia and delayed endochondral bone formation.
Weir E, Philbrick W, Amling M, Neff L, Baron R, Broadus A. Targeted overexpression of parathyroid hormone-related peptide in chondrocytes causes chondrodysplasia and delayed endochondral bone formation. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 10240-10245. PMID: 8816783, PMCID: PMC38368, DOI: 10.1073/pnas.93.19.10240.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone DevelopmentDwarfismGene Expression Regulation, DevelopmentalGrowth PlateHumansMiceMice, Inbred C57BLMice, Inbred StrainsMice, TransgenicOsteochondrodysplasiasParathyroid HormoneParathyroid Hormone-Related ProteinPolymerase Chain ReactionProcollagenPromoter Regions, GeneticProtein BiosynthesisProteinsRegulatory Sequences, Nucleic AcidTranscription, GeneticConceptsPTH/PTHrP receptorHormone-related peptideParathyroid hormonePTHrP receptorParathyroid hormone-related peptideChondrocyte differentiationOverexpression of PTHrPType II collagen promoterEndochondral ossificationShort-limbed dwarfismParaneoplastic hypercalcemiaPTHrP functionsBone collar formationMalignant tumorsDevelopmental regulatory moleculeEndochondral bone formationTransgenic micePTHrPCommon receptorEndochondral bone developmentTargeted overexpressionFetal tissuesPTHrP geneFollicle formationNormal boneOverexpression of Parathyroid Hormone-related Protein in the Pancreatic Islets of Transgenic Mice Causes Islet Hyperplasia, Hyperinsulinemia, and Hypoglycemia (∗)
Vasavada R, Cavaliere C, D'Ercole A, Dann P, Burtis W, Madlener A, Zawalich K, Zawalich W, Philbrick W, Stewart A. Overexpression of Parathyroid Hormone-related Protein in the Pancreatic Islets of Transgenic Mice Causes Islet Hyperplasia, Hyperinsulinemia, and Hypoglycemia (∗). Journal Of Biological Chemistry 1996, 271: 1200-1208. PMID: 8557651, DOI: 10.1074/jbc.271.2.1200.Peer-Reviewed Original ResearchConceptsRat insulin II promoterInsulin secretionIslet massPancreatic isletsNormal littermatesHormone-related proteinBlood glucose valuesTotal islet massIslet perifusion studiesNormal physiologic roleInappropriate hyperinsulinemiaParathyroid hormoneIslet hyperplasiaInsulin concentrationsTotal islet numberAutocrine roleGlucose homeostasisPerifusion studiesTransgenic miceGlucose valuesIslet numberIslet cellsPhysiologic rolePTHrPMice
1989
Functional and Molecular Changes in Colony Stimulating Factor Secretion by Osteoblasts
Horowitz M, Einhorn T, Philbrick W, Yale R. Functional and Molecular Changes in Colony Stimulating Factor Secretion by Osteoblasts. Connective Tissue Research 1989, 20: 159-168. PMID: 2558840, DOI: 10.3109/03008208909023884.Peer-Reviewed Original Research