2022
Human dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis
Bhandari R, Yang H, Kosarek NN, Smith AE, Garlick JA, Hinchcliff M, Whitfield ML, Pioli PA. Human dermal fibroblast-derived exosomes induce macrophage activation in systemic sclerosis. Rheumatology 2022, 62: si114-si124. PMID: 35946522, PMCID: PMC9910573, DOI: 10.1093/rheumatology/keac453.Peer-Reviewed Original ResearchConceptsFibroblast-derived exosomesSSc patientsMacrophage activationGender-matched control subjectsSSc fibroblastsDonor-derived macrophagesReciprocal activationUpregulated surface expressionMHC class IICo-cultured macrophagesHealthy control fibroblastsExtracellular matrix depositionCell typesSystemic sclerosisHealthy ageIL-10Production of collagenIL-12p40IL-6Control subjectsSkin biopsiesSSc skinTherapeutic targetingClass IIFlow cytometry
2020
Profibrotic Activation of Human Macrophages in Systemic Sclerosis
Bhandari R, Ball MS, Martyanov V, Popovich D, Schaafsma E, Han S, ElTanbouly M, Orzechowski NM, Carns M, Arroyo E, Aren K, Hinchcliff M, Whitfield ML, Pioli PA. Profibrotic Activation of Human Macrophages in Systemic Sclerosis. Arthritis & Rheumatology 2020, 72: 1160-1169. PMID: 32134204, PMCID: PMC7329566, DOI: 10.1002/art.41243.Peer-Reviewed Original ResearchMeSH KeywordsAdultAntigens, CDAntigens, Differentiation, MyelomonocyticCell DifferentiationChemokine CCL2Coculture TechniquesFemaleFibroblastsFibrosisHLA-DR AntigensHumansImmunophenotypingInterleukin-6Lectins, C-TypeLeukocytes, MononuclearMacrophage ActivationMacrophagesMaleMannose ReceptorMannose-Binding LectinsMiddle AgedMonocytesPhosphorylationReceptor, Transforming Growth Factor-beta Type IReceptor, Transforming Growth Factor-beta Type IIReceptors, Cell SurfaceRNA, MessengerScleroderma, SystemicSkinSTAT3 Transcription FactorTranscriptomeTransforming Growth Factor betaConceptsPeripheral blood mononuclear cellsSystemic sclerosisSSc patientsBasal conditionsSex-matched healthy controlsSSc fibroblastsSurface markersHealthy donor monocytesBlood mononuclear cellsMediator of fibrosisInflammatory macrophage activationMonocyte-derived macrophagesActivation profilesGrowth factor βFibrotic activationGene expression signaturesDonor monocytesMononuclear cellsProfibrotic activationSkin fibrosisInterleukin-6Healthy controlsSSc skinIndependent cohortMacrophage activation
2016
Tenascin-C drives persistence of organ fibrosis
Bhattacharyya S, Wang W, Morales-Nebreda L, Feng G, Wu M, Zhou X, Lafyatis R, Lee J, Hinchcliff M, Feghali-Bostwick C, Lakota K, Budinger GR, Raparia K, Tamaki Z, Varga J. Tenascin-C drives persistence of organ fibrosis. Nature Communications 2016, 7: 11703. PMID: 27256716, PMCID: PMC4895803, DOI: 10.1038/ncomms11703.Peer-Reviewed Original ResearchConceptsSystemic sclerosisToll-like receptorsOrgan fibrosisFibrosis resolutionPathogenesis of SScTreatment of SScLevels of tenascinEndogenous danger signalsSSc skin biopsy samplesSkin biopsy samplesMechanism of actionLung fibrosisPathogenic roleTLR activatorsMouse modelBiopsy samplesFibroblast activationDanger signalsMyofibroblast transformationFibrosisSSc fibroblastsCollagen gene expressionSkin fibroblastsAmplification loopTenascin
2012
Imatinib mesylate causes genome-wide transcriptional changes in systemic sclerosis fibroblasts in vitro.
Hinchcliff M, Huang CC, Ishida W, Fang F, Lee J, Jafari N, Wilkes M, Bhattacharyya S, Leof E, Varga J. Imatinib mesylate causes genome-wide transcriptional changes in systemic sclerosis fibroblasts in vitro. Clinical And Experimental Rheumatology 2012, 30: s86-96. PMID: 22691216, PMCID: PMC3860597.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBiopsyCase-Control StudiesCells, CulturedFibroblastsFibrosisGene Expression ProfilingGene Expression RegulationHumansImatinib MesylateMiceMice, KnockoutOligonucleotide Array Sequence AnalysisPhosphorylationPiperazinesProtein Kinase InhibitorsProto-Oncogene Proteins c-ablPyrimidinesScleroderma, SystemicSignal TransductionSkinTime FactorsTranscription, GeneticTransforming Growth Factor beta1ConceptsSystemic sclerosisSSc fibroblastsSkin biopsiesInternal organ fibrosisHeterogeneous multifactorial diseaseControl fibroblastsControl skin biopsiesFibrotic gene expressionSystemic sclerosis fibroblastsC-AblProgressive skinAntifibrotic effectsImatinib mesylateHealthy controlsCardiovascular diseaseGene expressionHealthy subjectsFibrotic responseCholesterol metabolismOrgan fibrosisC-Abl activationMultifactorial diseaseTreatment resultsTissue levelsFibrosis