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
2015
Systems Level Analysis of Systemic Sclerosis Shows a Network of Immune and Profibrotic Pathways Connected with Genetic Polymorphisms
Mahoney JM, Taroni J, Martyanov V, Wood TA, Greene CS, Pioli PA, Hinchcliff ME, Whitfield ML. Systems Level Analysis of Systemic Sclerosis Shows a Network of Immune and Profibrotic Pathways Connected with Genetic Polymorphisms. PLOS Computational Biology 2015, 11: e1004005. PMID: 25569146, PMCID: PMC4288710, DOI: 10.1371/journal.pcbi.1004005.Peer-Reviewed Original ResearchConceptsGene-gene interaction networksGenetic risk lociInteraction networksGenome-wide gene expression datasetsRisk lociGene expression modulesSubset-specific genesExtracellular matrix remodelingGene expression datasetsExpression modulesSystemic sclerosisGene expressionGenetic polymorphismsIntrinsic subsetGenesSystem-level analysisExpression datasetsMatrix remodelingPolymorphic genesAntigen geneCell proliferationMultiple clinical cohortsOrgan fibrosisGene expression subsetsLoci
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