Fibroblasts; Myofibroblasts; Collagen

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Human fibroblasts synthesize elevated levels of extracellular matrix proteins in response to interleukin 4. The Journal of Clinical Investigation 1992; 90(4): 1479–1485. doi: 10.1172/JCI116015 Jinnin M, Ihn H, Yamane K, et al. Interleukin-13 stimulates the transcription of the human α2(I) collagen gene in human dermal fibroblasts. Journal of Biological Chemistry 2004; 279(40): 41783–41791. doi: 10.1074/jbc.M406951200 Kaviratne M, Hesse M, Leusink M, et al. IL-13 activates a mechanism of tissue fibrosis that is completely TGF-beta independent. The Journal of Immunology 2004; 173(6): 4020–4029. doi: 10.4049/jimmunol.173.6.4020 Hasegawa M, Sato S, Fujimoto M, et al. Serum levels of interleukin 6 (IL-6), oncostatin M, soluble IL-6 receptor, and soluble gp130 in patients with systemic sclerosis. The Journal of Rheumatology 1998; 25(2): 308–313. PMID: 9489824 O’Reilly S, Ciechomska M, Cant R, et al. 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Patients with systemic lupus erythematosus, myositis, rheumatoid arthritis and scleroderma share activation of a common type I interferon pathway. Annals of the Rheumatic Diseases 2011; 70(11): 2029–2036. Sharif R, Mayes MD, Tan FK, et al. IRF5 polymorphism predicts prognosis in patients with systemic sclerosis. Annals of the Rheumatic Diseases 2012; 71(7): 1197–1202. Christmann RB, Sampaio-Barros P, Stifano G, et al. Association of interferon- and transforming growth factor beta-regulated genes and macrophage activation with systemic sclerosis-related progressive lung fibrosis. Arthritis & Rheumatology 2014; 66(3): 714–725. doi: 10.1002/art.38288 Kajihara I, Jinnin M, Honda N, et al. Scleroderma dermal fibroblasts overexpress vascular endothelial growth factor due to autocrine transforming growth factor β signaling. Modern Rheumatology 2013; 23(3): 516–524. doi: 10.3109/s10165-012-0698-6 Maurer B, Distler A, Suliman YA, et al. Vascular endothelial growth factor aggravates fibrosis and vasculopathy in experimental models of systemic sclerosis. Annals of the Rheumatic Diseases 2014; 73(10): 1880–1887. Wei J, Melichian D, Komura K, et al. Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: A novel mouse model for scleroderma? Arthritis Rheum 2011; 63(6): 1707–1717. Dees C, Distler JH. Canonical Wnt signalling as a key regulator of fibrogenesis—Implications for targeted therapies? Experimental Dermatology 2013; 22(11): 710–713. doi: 10.1111/exd.12255 Horn A, Palumbo K, Cordazzo C, et al. Hedgehog signaling controls fibroblast activation and tissue fibrosis in systemic sclerosis. Arthritis & Rheumatology 2012; 64(8): 2724–2733. doi: 10.1002/art.34444 Hasegawa M, Sato S, Echigo T, et al. Up regulated expression of fractalkine/CX3CL1 and CX3CR1 in patients with systemic sclerosis. Annals of the Rheumatic Diseases 2005; 64(1): 21–28. Luong VH, Utsunomiya A, Chino T, et al. 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Breg cells are numerically decreased and functionally impaired in patients with systemic sclerosis. Arthritis & Rheumatology 2016; 68(2): 494–504. doi: 10.1002/art.39437 Fuschiotti P, Larregina AT, Ho J, et al. Interleukin-13-producing CD8+ T cells mediate dermal fibrosis in patients with systemic sclerosis. Arthritis & Rheumatology 2013; 65(1): 236–246. doi: 10.1002/art.37706 Pincha N, Hajam EY, Badarinath K, et al. PAI1 mediates fibroblast-mast cell interactions in skin fibrosis. The Journal of Clinical Investigation 2018; 128(5): 1807–1819. doi: 10.1172/JCI99088 Altorok N, Tsou PS, Coit P, et al. Genome-wide DNA methylation analysis in dermal fibroblasts from patients with diffuse and limited systemic sclerosis reveals common and subset-specific DNA methylation aberrancies. Annals of the Rheumatic Diseases 2015; 74(8): 1612–1620. Huber LC, Distler JH, Moritz F, et al. 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