2023
IL-6 trans-signaling in a humanized mouse model of scleroderma
Odell I, Agrawal K, Sefik E, Odell A, Caves E, Kirkiles-Smith N, Horsley V, Hinchcliff M, Pober J, Kluger Y, Flavell R. IL-6 trans-signaling in a humanized mouse model of scleroderma. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2306965120. PMID: 37669366, PMCID: PMC10500188, DOI: 10.1073/pnas.2306965120.Peer-Reviewed Original ResearchConceptsBone marrow-derived immune cellsIL-6Human hematopoietic stem cellsImmune cellsT cellsScleroderma skinSoluble IL-6 receptorCD8 T cellsHumanized mouse modelPathogenesis of sclerodermaMesenchymal cellsFibroblast-derived IL-6IL-6 receptorIL-6 signalingT cell activationHuman IL-6Human T cellsExpression of collagenFibrosis improvementPansclerotic morpheaHuman endothelial cellsHumanized miceReduced markersSkin graftsHuman CD4
2012
Wnt/β‐catenin signaling is hyperactivated in systemic sclerosis and induces Smad‐dependent fibrotic responses in mesenchymal cells
Wei J, Fang F, Lam AP, Sargent JL, Hamburg E, Hinchcliff ME, Gottardi CJ, Atit R, Whitfield ML, Varga J. Wnt/β‐catenin signaling is hyperactivated in systemic sclerosis and induces Smad‐dependent fibrotic responses in mesenchymal cells. Arthritis & Rheumatism 2012, 64: 2734-2745. PMID: 22328118, PMCID: PMC3553791, DOI: 10.1002/art.34424.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAdultBeta CateninBiopsyCase-Control StudiesCell MovementCell ProliferationCells, CulturedFibroblastsFibrosisFrizzled ReceptorsHumansIntercellular Signaling Peptides and ProteinsLymphoid Enhancer-Binding Factor 1MesodermRepressor ProteinsScleroderma, SystemicSignal TransductionSkinSmad ProteinsWnt ProteinsWnt3A ProteinConceptsWnt/β-cateninCanonical WntWnt-3aMesenchymal cellsGenome-wide expression dataAberrant Wnt/β-catenin pathway activationCell fate specificationΒ-cateninSkin biopsy specimensMyofibroblast differentiationCanonical Wnt/β-cateninWnt/β-catenin signalingWnt receptor Fzd2Subcutaneous preadipocytesSystemic sclerosisΒ-catenin signalingFate specificationBiopsy specimensΒ-catenin activationExpression of WntHuman mesenchymal cellsGrowth factor βPathway componentsGene expressionProfibrotic responses
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