2014
FibronectinEDA Promotes Chronic Cutaneous Fibrosis Through Toll-Like Receptor Signaling
Bhattacharyya S, Tamaki Z, Wang W, Hinchcliff M, Hoover P, Getsios S, White ES, Varga J. FibronectinEDA Promotes Chronic Cutaneous Fibrosis Through Toll-Like Receptor Signaling. Science Translational Medicine 2014, 6: 232ra50. PMID: 24739758, PMCID: PMC4414050, DOI: 10.1126/scitranslmed.3008264.Peer-Reviewed Original ResearchConceptsToll-like receptor 4Endogenous TLR4 ligandsCutaneous fibrosisTLR4 ligandToll-like receptor signalingProgressive autoimmune diseaseLesional skin biopsiesFibronectin extra domain ATreatment of fibrosisTissue repair responseHallmark of sclerodermaPersistent fibroblast activationExtra domain ATLR4 blockadeAutoimmune diseasesChronic conditionsChronic fibrosisReceptor 4Skin biopsiesFibrotic responseOrganotypic skin equivalentsMultiple organsPotent stimulusSclerodermaFibroblast activation
2011
Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: A novel mouse model for scleroderma?
Wei J, Melichian D, Komura K, Hinchcliff M, Lam AP, Lafyatis R, Gottardi CJ, MacDougald OA, Varga J. Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: A novel mouse model for scleroderma? Arthritis & Rheumatism 2011, 63: 1707-1717. PMID: 21370225, PMCID: PMC3124699, DOI: 10.1002/art.30312.Peer-Reviewed Original ResearchConceptsSystemic sclerosisSubcutaneous adipose tissueTransgenic miceWnt-10bBiopsy specimensDermal fibrosisMouse modelAdipose tissueLesional skin biopsy specimensSkin biopsy specimensNovel mouse modelMesenchymal cellsSmooth muscle actin gene expressionSkin fibroblastsNovel animal modelFibrotic gene expressionWnt/β-catenin signalingSetting of fibrosisGrowth factor βΒ-catenin signalingPulmonary fibrosisSubcutaneous lipoatrophySkin fibrosisGene expressionMyofibroblast accumulation
2009
A non-Smad mechanism of fibroblast activation by transforming growth factor-β via c-Abl and Egr-1: selective modulation by imatinib mesylate
Bhattacharyya S, Ishida W, Wu M, Wilkes M, Mori Y, Hinchcliff M, Leof E, Varga J. A non-Smad mechanism of fibroblast activation by transforming growth factor-β via c-Abl and Egr-1: selective modulation by imatinib mesylate. Oncogene 2009, 28: 1285-1297. PMID: 19151753, PMCID: PMC4006376, DOI: 10.1038/onc.2008.479.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzamidesBleomycinCells, CulturedCollagenEarly Growth Response Protein 1Extracellular Signal-Regulated MAP KinasesFibroblastsFibrosisHumansImatinib MesylateMiceMice, Inbred BALB CNIH 3T3 CellsPiperazinesProtein Kinase InhibitorsProto-Oncogene Proteins c-ablPyrimidinesSignal TransductionSmad2 ProteinSmad3 ProteinTransforming Growth Factor betaConceptsChronic myelogenous leukemiaFibrotic responseEgr-1Growth factorUpregulated tissue expressionFibrosis of skinNovel therapeutic approachesEarly growth response factor-1Kinase-deficient mutant formC-AblNormal fibroblastsTGF-β stimulationIntracellular signaling mechanismLesional skinStimulation of collagenImatinib mesylateMouse embryonic fibroblastsFibrotic processMyelogenous leukemiaTherapeutic approachesPharmacological targetingTarget of inhibitionTGF-β responseFibroblast activationC-Abl activation