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Review

Updates on the pathophysiology of dermal sclerosis

Pages 559-568 | Published online: 10 Jan 2014

References

  • Yamamoto T. Scleroderma – pathophysiology. Eur. J. Dermatol. 19(1), 14–24 (2009).
  • Beyer C, Schett G, Distler O, Distler JH. Animal models of systemic sclerosis: prospects and limitations. Arthritis Rheum. 62(10), 2831–2844 (2010).
  • Radstake TR, van Bon L, Broen J et al. Increased frequency and compromised function of T regulatory cells in systemic sclerosis (SSc) is related to a diminished CD69 and TGFβ expression. PLoS ONE 4(6), e5981 (2009).
  • Slobodin G, Ahmad MS, Rosner I et al. Regulatory T cells (CD4(+)CD25(bright)FoxP3(+)) expansion in systemic sclerosis correlates with disease activity and severity. Cell. Immunol. 261(2), 77–80 (2010).
  • Antiga E, Quaglino P, Bellandi S et al. Regulatory T cells in the skin lesions and blood of patients with systemic sclerosis and morphoea. Br. J. Dermatol. 162(5), 1056–1063 (2010).
  • Higashi-Kuwata N, Jinnin M, Makino T et al. Characterization of monocyte/macrophage subsets in the skin and peripheral blood derived from patients with systemic sclerosis. Arthritis Res. Ther. 12(4), R128 (2010).
  • Martinez FO, Helming L, Gordon S. Alternative activation of macrophages: an immunologic functional perspective. Annu. Rev. Immunol. 27, 451–483 (2009).
  • Sato S, Fujimoto M, Hasegawa M, Takehara K. Altered blood B lymphocyte homeostasis in systemic sclerosis: expanded naive B cells and diminished but activated memory B cells. Arthritis Rheum. 50(6), 1918–1927 (2004).
  • Smith V, Van Praet JT, Vandooren B et al. Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study. Ann. Rheum. Dis. 69(1), 193–197 (2010).
  • Daoussis D, Liossis SN, Tsamandas AC et al. Experience with rituximab in scleroderma: results from a 1-year, proof-of-principle study. Rheumatology (Oxford). 49(2), 271–280 (2010).
  • Bosello S, De Santis M, Lama G et al. B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial. Arthritis Res. Ther. 12(2), R54 (2010).
  • Daoussis D, Tsamandas AC, Liossis SN et al. B-cell depletion therapy in patients with diffuse systemic sclerosis associates with a significant decrease in PDGFR expression and activation in spindle-like cells in the skin. Arthritis Res. Ther. 14(3), R145 (2012).
  • Hasegawa M, Hamaguchi Y, Yanaba K et al. B-lymphocyte depletion reduces skin fibrosis and autoimmunity in the tight-skin mouse model for systemic sclerosis. Am. J. Pathol. 169(3), 954–966 (2006).
  • Broen JC, Coenen MJ, Radstake TR. Genetics of systemic sclerosis: an update. Curr. Rheumatol. Rep. 14(1), 11–21 (2012).
  • Kawakami T, Ihn H, Xu W, Smith E, LeRoy C, Trojanowska M. Increased expression of TGF-β receptors by scleroderma fibroblasts: evidence for contribution of autocrine TGF-β signaling to scleroderma phenotype. J. Invest. Dermatol. 110(1), 47–51 (1998).
  • Kubo M, Ihn H, Yamane K, Tamaki K. Up-regulated expression of transforming growth factor β receptors in dermal fibroblasts in skin sections from patients with localized scleroderma. Arthritis Rheum. 44(3), 731–734 (2001).
  • Dong C, Zhu S, Wang T et al. Deficient Smad7 expression: a putative molecular defect in scleroderma. Proc. Natl Acad. Sci. USA 99(6), 3908–3913 (2002).
  • Asano Y, Ihn H, Yamane K, Kubo M, Tamaki K. Impaired Smad7-Smurf-mediated negative regulation of TGF-β signaling in scleroderma fibroblasts. J. Clin. Invest. 113(2), 253–264 (2004).
  • Morris E, Chrobak I, Bujor A et al. Endoglin promotes TGF-b/Smad1 signaling in scleroderma fibroblasts. J. Cell. Physiol. 226(12), 3340–3348 (2011).
  • Varga J, Whitfield ML. Transforming growth factor-β in systemic sclerosis (scleroderma). Front. Biosci. (Schol. Ed.) 1, 226–235 (2009).
  • Samuel GH, Bujor AM, Nakerakanti SS, Hant FN, Trojanowska M. Autocrine transforming growth factor b signaling regulates extracellular signal-regulated kinase ½ phosphorylation via modulation of protein phosphatase 2A expression in scleroderma fibroblasts. Fibrogenesis Tissue Repair 3, 25 (2010).
  • Bhattacharyya S, Chen SJ, Wu M et al. Smad-independent transforming growth factor-β regulation of early growth response-1 and sustained expression in fibrosis: implications for scleroderma. Am. J. Pathol. 173(4), 1085–1099 (2008).
  • Bhattacharyya S, Sargent JL, Du P et al. Egr-1 induces a profibrotic injury/repair gene program associated with systemic sclerosis. PLoS ONE 6(9), e23082 (2011).
  • Fang F, Ooka K, Bhattacharyya S et al. The early growth response gene EGR2 (Alias Krox20) is a novel transcriptional target of transforming growth factor-b that is up-regulated in systemic sclerosis and mediates profibrotic responses. Am. J. Pathol. 178(5), 2077–2090 (2011).
  • Holmes AM, Ponticos M, Shi-Wen X, Denton CP, Abraham DJ. Elevated CCN2 expression in scleroderma: a putative role for the TGFb accessory receptors TGFbRIII and endoglin. J. Cell Commun. Signal. 5(3), 173–177 (2011).
  • Sonnylal S, Shi-Wen X, Leoni P et al. Selective expression of connective tissue growth factor in fibroblasts in vivo promotes systemic tissue fibrosis. Arthritis Rheum. 62(5), 1523–1532 (2010).
  • Holmes A, Abraham DJ, Chen Y et al. Constitutive connective tissue growth factor expression in scleroderma fibroblasts is dependent on Sp1. J. Biol. Chem. 278(43), 41728–41733 (2003).
  • Sato S, Nagaoka T, Hasegawa M et al. Serum levels of connective tissue growth factor are elevated in patients with systemic sclerosis: association with extent of skin sclerosis and severity of pulmonary fibrosis. J. Rheumatol. 27(1), 149–154 (2000).
  • Ishibuchi H, Abe M, Yokoyama Y, Ishikawa O. Induction of matrix metalloproteinase-1 by small interfering RNA targeting connective tissue growth factor in dermal fibroblasts from patients with systemic sclerosis. Exp. Dermatol. 19(8), 111–116 (2010).
  • Yamamoto T. Chemokines and chemokine receptors in scleroderma. Int. Arch. Allergy Immunol. 140(4), 345–356 (2006).
  • Gharaee-Kermani M, Denholm EM, Phan SH. Costimulation of fibroblast collagen and transforming growth factor β1 gene expression by monocyte chemoattractant protein-1 via specific receptors. J. Biol. Chem. 271(30), 17779–17784 (1996).
  • Yamamoto T, Eckes B, Mauch C, Hartmann K, Krieg T. Monocyte chemoattractant protein-1 enhances gene expression and synthesis of matrix metalloproteinase-1 in human fibroblasts by an autocrine IL-1α loop. J. Immunol. 164(12), 6174–6179 (2000).
  • Galindo M, Santiago B, Rivero M, Rullas J, Alcami J, Pablos JL. Chemokine expression by systemic sclerosis fibroblasts: abnormal regulation of monocyte chemoattractant protein 1 expression. Arthritis Rheum. 44(6), 1382–1386 (2001).
  • Hasegawa M, Sato S, Takehara K. Augmented production of chemokines (monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α (MIP-1α) and MIP-1β) in patients with systemic sclerosis: MCP-1 and MIP-1α may be involved in the development of pulmonary fibrosis. Clin. Exp. Immunol. 117(1), 159–165 (1999).
  • Yamamoto T, Eckes B, Hartmann K, Krieg T. Expression of monocyte chemoattractant protein-1 in the lesional skin of systemic sclerosis. J. Dermatol. Sci. 26(2), 133–139 (2001).
  • Distler O, Pap T, Kowal-Bielecka O et al. Overexpression of monocyte chemoattractant protein 1 in systemic sclerosis: role of platelet-derived growth factor and effects on monocyte chemotaxis and collagen synthesis. Arthritis Rheum. 44(11), 2665–2678 (2001).
  • Yamamoto T, Eckes B, Krieg T. High expression and autoinduction of monocyte chemoattractant protein-1 in scleroderma fibroblasts. Eur. J. Immunol. 31(10), 2936–2941 (2001).
  • Zhu Z, Ma B, Zheng T et al. IL-13-induced chemokine responses in the lung: role of CCR2 in the pathogenesis of IL-13-induced inflammation and remodeling. J. Immunol. 168(6), 2953–2962 (2002).
  • Greenblatt MB, Sargent JL, Farina G et al. Interspecies comparison of human and murine scleroderma reveals IL-13 and CCL2 as disease subset-specific targets. Am. J. Pathol. 180(3), 1080–1094 (2012).
  • Yamamoto T, Nishioka K. Role of monocyte chemoattractant protein-1 and its receptor, CCR-2, in the pathogenesis of bleomycin-induced scleroderma. J. Invest. Dermatol. 121(3), 510–516 (2003).
  • Chujo S, Shirasaki F, Kondo-Miyazaki M, Ikawa Y, Takehara K. Role of connective tissue growth factor and its interaction with basic fibroblast growth factor and macrophage chemoattractant protein-1 in skin fibrosis. J. Cell. Physiol. 220(1), 189–195 (2009).
  • Carulli MT, Ong VH, Ponticos M et al. Chemokine receptor CCR2 expression by systemic sclerosis fibroblasts: evidence for autocrine regulation of myofibroblast differentiation. Arthritis Rheum. 52(12), 3772–3782 (2005).
  • Yamamoto T. Pathogenic role of CCL2/MCP-1 in scleroderma. Front. Biosci. 13, 2686–2695 (2008).
  • Distler JH, Akhmetshina A, Schett G, Distler O. Monocyte chemoattractant proteins in the pathogenesis of systemic sclerosis. Rheumatology (Oxford). 48(2), 98–103 (2009).
  • Kitaba S, Murota H, Terao M et al. Blockade of interleukin-6 receptor alleviates disease in mouse model of scleroderma. Am. J. Pathol. 180(1), 165–176 (2012).
  • Shima Y, Kuwahara Y, Murota H et al. The skin of patients with systemic sclerosis softened during the treatment with anti-IL-6 receptor antibody tocilizumab. Rheumatology (Oxford) 49(12), 2408–2412 (2010).
  • Le Huu D, Matsushita T, Jin G et al. IL-6 blockade attenuates the development of murine sclerodermatous chronic graft-versus-host disease. J. Invest. Dermatol. 132(12), 2752–2761(2012).
  • Van Praet JT, Smith V, Haspeslagh M, Degryse N, Elewaut D, De Keyser F. Histopathological cutaneous alterations in systemic sclerosis: a clinicopathological study. Arthritis Res. Ther. 13(1), R35 (2011).
  • Baroni SS, Santillo M, Bevilacqua F et al. Stimulatory autoantibodies to the PDGF receptor in systemic sclerosis. N. Engl. J. Med. 354(25), 2667–2676 (2006).
  • Motegi S, Garfield S, Feng X, Sárdy M, Udey MC. Potentiation of platelet-derived growth factor receptor-b signaling mediated by integrin-associated MFG-E8. Arterioscler. Thromb. Vasc. Biol. 31(11), 2653–2664 (2011).
  • Maurer B, Busch N, Jüngel A et al. Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis. Circulation 120(23), 2367–2376 (2009).
  • Kuwana M, Okazaki Y, Yasuoka H, Kawakami Y, Ikeda Y. Defective vasculogenesis in systemic sclerosis. Lancet 364(9434), 603–610 (2004).
  • Yamaguchi Y, Okazaki Y, Seta N et al. Enhanced angiogenic potency of monocytic endothelial progenitor cells in patients with systemic sclerosis. Arthritis Res. Ther. 12(6), R205 (2010).
  • Horstmeyer A, Licht C, Scherr G, Eckes B, Krieg T. Signalling and regulation of collagen I synthesis by ET-1 and TGF-β1. FEBS J. 272(24), 6297–6309 (2005).
  • Shi-Wen X, Denton CP, Dashwood MR et al. Fibroblast matrix gene expression and connective tissue remodeling: role of endothelin-1. J. Invest. Dermatol. 116(3), 417–425 (2001).
  • Shephard P, Hinz B, Smola-Hess S, Meister JJ, Krieg T, Smola H. Dissecting the roles of endothelin, TGF-β and GM-CSF on myofibroblast differentiation by keratinocytes. Thromb. Haemost. 92(2), 262–274 (2004).
  • Vancheeswaran R, Magoulas T, Efrat G et al. Circulating endothelin-1 levels in systemic sclerosis subsets – a marker of fibrosis or vascular dysfunction? J. Rheumatol. 21(10), 1838–1844 (1994).
  • Shi-Wen X, Chen Y, Denton CP et al. Endothelin-1 promotes myofibroblast induction through the ETA receptor via a rac/phosphoinositide 3-kinase/Akt-dependent pathway and is essential for the enhanced contractile phenotype of fibrotic fibroblasts. Mol. Biol. Cell 15(6), 2707–2719 (2004).
  • Hirata Y, Emori T, Eguchi S et al. Endothelin receptor subtype B mediates synthesis of nitric oxide by cultured bovine endothelial cells. J. Clin. Invest. 91(4), 1367–1373 (1993).
  • Yamamoto T, Katayama I, Nishioka K. Nitric oxide production and inducible nitric oxide synthase expression in systemic sclerosis. J. Rheumatol. 25(2), 314–317 (1998).
  • Beyer C, Schett G, Gay S, Distler O, Distler JH. Hypoxia. Hypoxia in the pathogenesis of systemic sclerosis. Arthritis Res. Ther. 11(2), 220 (2009).
  • Kubo M, Czuwara-Ladykowska J, Moussa O et al. Persistent down-regulation of Fli1, a suppressor of collagen transcription, in fibrotic scleroderma skin. Am. J. Pathol. 163(2), 571–581 (2003).
  • Asano Y, Stawski L, Hant F et al. Endothelial Fli1 deficiency impairs vascular homeostasis: a role in scleroderma vasculopathy. Am. J. Pathol. 176(4), 1983–1998 (2010).
  • Bujor AM, Asano Y, Haines P, Lafyatis R, Trojanowska M. The c-Abl tyrosine kinase controls protein kinase Cd-induced Fli-1 phosphorylation in human dermal fibroblasts. Arthritis Rheum. 63(6), 1729–1737 (2011).
  • Agarwal SK, Wu M, Livingston CK et al. Toll-like receptor 3 upregulation by type I interferon in healthy and scleroderma dermal fibroblasts. Arthritis Res. Ther. 13(1), R3 (2011).
  • Gailit J, Marchese MJ, Kew RR, Gruber BL. The differentiation and function of myofibroblasts is regulated by mast cell mediators. J. Invest. Dermatol. 117(5), 1113–1119 (2001).
  • Quan TE, Cowper S, Wu SP, Bockenstedt LK, Bucala R. Circulating fibrocytes: collagen-secreting cells of the peripheral blood. Int. J. Biochem. Cell Biol. 36(4), 598–606 (2004).
  • Katebi M, Fernandez P, Chan ES, Cronstein BN. Adenosine A2A receptor blockade or deletion diminishes fibrocyte accumulation in the skin in a murine model of scleroderma, bleomycin-induced fibrosis. Inflammation 31(5), 299–303 (2008).
  • Maurer B, Stanczyk J, Jüngel A et al. MicroRNA-29, a key regulator of collagen expression in systemic sclerosis. Arthritis Rheum. 62(6), 1733–1743 (2010).
  • Honda N, Jinnin M, Kajihara I et al. TGF-b-mediated downregulation of microRNA-196a contributes to the constitutive upregulated type I collagen expression in scleroderma dermal fibroblasts. J. Immunol. 188(7), 3323–3331 (2012).
  • Nakamura M, Tokura Y. Expression of SNAI1 and TWIST1 in the eccrine glands of patients with systemic sclerosis: possible involvement of epithelial-mesenchymal transition in the pathogenesis. Br. J. Dermatol. 164(1), 204–205 (2011).
  • Aden N, Nuttall A, Shiwen X et al. Epithelial cells promote fibroblast activation via IL-1α in systemic sclerosis. J. Invest. Dermatol. 130(9), 2191–2200 (2010).
  • Palumbo K, Zerr P, Tomcik M et al. The transcription factor JunD mediates transforming growth factor {β}-induced fibroblast activation and fibrosis in systemic sclerosis. Ann. Rheum. Dis. 70(7), 1320–1326 (2011).
  • Avouac J, Palumbo K, Tomcik M et al. Inhibition of activator protein 1 signaling abrogates transforming growth factor b-mediated activation of fibroblasts and prevents experimental fibrosis. Arthritis Rheum. 64(5), 1642–1652 (2012).
  • Beyer C, Schramm A, Akhmetshina A et al. β-catenin is a central mediator of pro-fibrotic Wnt signaling in systemic sclerosis. Ann. Rheum. Dis. 71(5), 761–767 (2012).
  • Bergmann C, Akhmetshina A, Dees C et al. Inhibition of glycogen synthase kinase 3ß induces dermal fibrosis by activation of the canonical Wnt pathway. Ann. Rheum. Dis. 70(12), 2191–2198 (2011).
  • Jelaska A, Korn JH. Role of apoptosis and transforming growth factor β1 in fibroblast selection and activation in systemic sclerosis. Arthritis Rheum. 43(10), 2230–2239 (2000).
  • Santiago B, Galindo M, Rivero M, Pablos JL. Decreased susceptibility to Fas-induced apoptosis of systemic sclerosis dermal fibroblasts. Arthritis Rheum. 44(7), 1667–1676 (2001).
  • Sgonc R, Gruschwitz MS, Dietrich H, Recheis H, Gershwin ME, Wick G. Endothelial cell apoptosis is a primary pathogenetic event underlying skin lesions in avian and human scleroderma. J. Clin. Invest. 98(3), 785–792 (1996).
  • Zhang HY, Phan SH. Inhibition of myofibroblast apoptosis by transforming growth factor β(1). Am. J. Respir. Cell Mol. Biol. 21(6), 658–665 (1999).
  • Laplante P, Raymond MA, Gagnon G et al. Novel fibrogenic pathways are activated in response to endothelial apoptosis: implications in the pathophysiology of systemic sclerosis. J. Immunol. 174(9), 5740–5749 (2005).
  • Barnes TC, Spiller DG, Anderson ME, Edwards SW, Moots RJ. Endothelial activation and apoptosis mediated by neutrophil-dependent interleukin 6 trans-signalling: a novel target for systemic sclerosis? Ann. Rheum. Dis. 70(2), 366–372 (2011).
  • Wetzig T, Petri JB, Mittag M, Haustein UF. Serum levels of soluble Fas/APO-1 receptor are increased in systemic sclerosis. Arch. Dermatol. Res. 290(4), 187–190 (1998).
  • Stummvoll GH, Aringer M, Smolen JS et al. Derangement of apoptosis-related lymphocyte homeostasis in systemic sclerosis. Rheumatology (Oxford) 39(12), 1341–1350 (2000).
  • Bianchi T, Bardazzi F, Patrizi A. Soluble Fas levels in patients with systemic sclerosis. Arch. Dermatol. Res. 292(10), 522–523 (2000).
  • Ates A, Kinikli G, Turgay M, Duman M. The levels of serum-soluble Fas in patients with rheumatoid arthritis and systemic sclerosis. Clin. Rheumatol. 23(5), 421–425 (2004).
  • Kessel A, Rosner I, Rozenbaum M et al. Increased CD8+ T-cell apoptosis in scleroderma is associated with low levels of NF-κB. J. Clin. Immunol. 24(1), 30–36 (2004).
  • Jun JB, Kuechle M, Min J et al. Scleroderma fibroblasts demonstrate enhanced activation of Akt (protein kinase B) in situ. J. Invest. Dermatol. 124(2), 298–303 (2005).
  • Yamamoto T. Autoimmune mechanisms of scleroderma and a role of oxidative stress. Self Nonself. 2(1), 4–10 (2011).
  • Avouac J, Borderie D, Ekindjian OG, Kahan A, Allanore Y. High DNA oxidative damage in systemic sclerosis. J. Rheumatol. 37(12), 2540–2547 (2010).
  • Murrell GA, Francis MJ, Bromley L. Modulation of fibroblast proliferation by oxygen free radicals. Biochem. J. 265(3), 659–665 (1990).
  • Falanga V, Martin TA, Takagi H et al. Low oxygen tension increases mRNA levels of α 1 (I) procollagen in human dermal fibroblasts. J. Cell. Physiol. 157(2), 408–412 (1993).
  • Casciola-Rosen L, Wigley F, Rosen A. Scleroderma autoantigens are uniquely fragmented by metal-catalyzed oxidation reactions: implications for pathogenesis. J. Exp. Med. 185(1), 71–79 (1997).
  • Sambo P, Baroni SS, Luchetti M et al. Oxidative stress in scleroderma: maintenance of scleroderma fibroblast phenotype by the constitutive up-regulation of reactive oxygen species generation through the NADPH oxidase complex pathway. Arthritis Rheum. 44(11), 2653–2664 (2001).
  • Galindo M, Santiago B, Alcami J, Rivero M, Martín-Serrano J, Pablos JL. Hypoxia induces expression of the chemokines monocyte chemoattractant protein-1 (MCP-1) and IL-8 in human dermal fibroblasts. Clin. Exp. Immunol. 123(1), 36–41 (2001).
  • Servettaz A, Goulvestre C, Kavian N et al. Selective oxidation of DNA topoisomerase 1 induces systemic sclerosis in the mouse. J. Immunol. 182(9), 5855–5864 (2009).
  • Yamakage A, Kikuchi K, Smith EA, LeRoy EC, Trojanowska M. Selective upregulation of platelet-derived growth factor α receptors by transforming growth factor β in scleroderma fibroblasts. J. Exp. Med. 175(5), 1227–1234 (1992).
  • Klareskog L, Gustafsson R, Scheynius A, Hällgren R. Increased expression of platelet-derived growth factor type B receptors in the skin of patients with systemic sclerosis. Arthritis Rheum. 33(10), 1534–1541 (1990).
  • Xue-yi Z, Jian-Zhong Z, Ping T, Sheng-Qing M. Expression of platelet-derived growth factor B-chain and platelet-derived growth factor β-receptor in fibroblasts of scleroderma. J. Dermatol. Sci. 18, 90–97 (1998).
  • Tsou PS, Talia NN, Pinney AJ et al. Effect of oxidative stress on protein tyrosine phosphatase 1B in scleroderma dermal fibroblasts. Arthritis Rheum. 64(6), 1978–1989 (2012).
  • Classen JF, Henrohn D, Rorsman F et al. Lack of evidence of stimulatory autoantibodies to platelet-derived growth factor receptor in patients with systemic sclerosis. Arthritis Rheum. 60(4), 1137–1144 (2009).
  • Avouac J, Fürnrohr BG, Tomcik M et al. Inactivation of the transcription factor STAT-4 prevents inflammation-driven fibrosis in animal models of systemic sclerosis. Arthritis Rheum. 63(3), 800–809 (2011).
  • Burt RK, Shah SJ, Dill K et al. Autologous non-myeloablative haemopoietic stem-cell transplantation compared with pulse cyclophosphamide once per month for systemic sclerosis (ASSIST): an open-label, randomised Phase 2 trial. Lancet 378(9790), 498–506 (2011).
  • Yamamoto T. Animal model of systemic sclerosis. J. Dermatol. 37(1), 26–41 (2010).
  • Yamamoto T, Takagawa S, Katayama I, Nishioka K. Anti-sclerotic effect of transforming growth factor-β antibody in a mouse model of bleomycin-induced scleroderma. Clin. Immunol. 92(1), 6–13 (1999).
  • Santiago B, Gutierrez-Cañas I, Dotor J et al. Topical application of a peptide inhibitor of transforming growth factor-β1 ameliorates bleomycin-induced skin fibrosis. J. Invest. Dermatol. 125(3), 450–455 (2005).
  • Nakamura-Wakatsuki T, Oyama N, Yamamoto T. Local injection of latency-associated peptide, a linker propeptide specific for active form of transforming growth factor-β1, inhibits dermal sclerosis in bleomycin-induced murine scleroderma. Exp. Dermatol. 21(3), 189–194 (2012).
  • Wu MH, Yokozeki H, Takagawa S et al. Hepatocyte growth factor both prevents and ameliorates the symptoms of dermal sclerosis in a mouse model of scleroderma. Gene Ther. 11(2), 170–180 (2004).
  • Yamamoto T, Takagawa S, Katayama I, Mizushima Y, Nishioka K. Effect of superoxide dismutase on bleomycin-induced dermal sclerosis: implications for the treatment of systemic sclerosis. J. Invest. Dermatol. 113(5), 843–847 (1999).
  • Kokot A, Sindrilaru A, Schiller M et al. α-Melanocyte-stimulating hormone suppresses bleomycin-induced collagen synthesis and reduces tissue fibrosis in a mouse model of scleroderma: melanocortin peptides as a novel treatment strategy for scleroderma? Arthritis Rheum. 60(2), 592–603 (2009).
  • Yamamoto T, Takagawa S, Kuroda M, Nishioka K. Effect of interferon-γ on experimental scleroderma induced by bleomycin. Arch. Dermatol. Res. 292(7), 362–365 (2000).
  • Kimura M, Kawahito Y, Hamaguchi M et al. SKL-2841, a dual antagonist of MCP-1 and MIP-1 β, prevents bleomycin-induced skin sclerosis in mice. Biomed. Pharmacother. 61(4), 222–228 (2007).
  • Kajii M, Suzuki C, Kashihara J et al. Prevention of excessive collagen accumulation by human intravenous immunoglobulin treatment in a murine model of bleomycin-induced scleroderma. Clin. Exp. Immunol. 163(2), 235–241 (2011).
  • Distler JH, Jüngel A, Huber LC et al. Imatinib mesylate reduces production of extracellular matrix and prevents development of experimental dermal fibrosis. Arthritis Rheum. 56(1), 311–322 (2007).
  • Koca SS, Isik A, Ozercan IH, Ustundag B, Evren B, Metin K. Effectiveness of etanercept in bleomycin-induced experimental scleroderma. Rheumatology (Oxford) 47(2), 172–175 (2008).
  • Terao M, Murota H, Kitaba S, Katayama I. Tumor necrosis factor-α processing inhibitor-1 inhibits skin fibrosis in a bleomycin-induced murine model of scleroderma. Exp. Dermatol. 19(1), 38–43 (2010).
  • Akhmetshina A, Dees C, Pileckyte M et al. Dual inhibition of c-abl and PDGF receptor signaling by dasatinib and nilotinib for the treatment of dermal fibrosis. FASEB J. 22(7), 2214–2222 (2008).
  • Kawai M, Masuda A, Kuwana M. A CD40-CD154 interaction in tissue fibrosis. Arthritis Rheum. 58(11), 3562–3573 (2008).
  • Yamamoto T, Nishioka K. Possible role of apoptosis in the pathogenesis of bleomycin-induced scleroderma. J. Invest. Dermatol. 122(1), 44–50 (2004).
  • Yoshizaki A, Yanaba K, Yoshizaki A et al. Treatment with rapamycin prevents fibrosis in tight-skin and bleomycin-induced mouse models of systemic sclerosis. Arthritis Rheum. 62(8), 2476–2487 (2010).
  • Ikeda H, Sunazuka T, Suzuki H et al. EM703, the new derivative of erythromycin, inhibits transcription of type I collagen in normal and scleroderma fibroblasts. J. Dermatol. Sci. 49(3), 195–205 (2008).
  • Wu M, Melichian DS, Chang E, Warner-Blankenship M, Ghosh AK, Varga J. Rosiglitazone abrogates bleomycin-induced scleroderma and blocks profibrotic responses through peroxisome proliferator-activated receptor-γ. Am. J. Pathol. 174(2), 519–533 (2009).
  • Chan ES, Fernandez P, Merchant AA et al. Adenosine A2A receptors in diffuse dermal fibrosis: pathogenic role in human dermal fibroblasts and in a murine model of scleroderma. Arthritis Rheum. 54(8), 2632–2642 (2006).
  • Balistreri E, Garcia-Gonzalez E, Selvi E et al. The cannabinoid WIN55, 212-2 abrogates dermal fibrosis in scleroderma bleomycin model. Ann. Rheum. Dis. 70(4), 695–699 (2011).
  • Hasegawa M, Matsushita Y, Horikawa M et al. A novel inhibitor of Smad-dependent transcriptional activation suppresses tissue fibrosis in mouse models of systemic sclerosis. Arthritis Rheum. 60(11), 3465–3475 (2009).
  • Avouac J, Palumbo K, Tomcik M et al. Inhibition of AP-1 signaling abrogates TGF-β mediated activation of fibroblasts and prevents experimental fibrosis. Arthritis Rheum. 64(5), 1642–1652 (2011).
  • Dees C, Zerr P, Tomcik M et al. Inhibition of notch signaling prevents experimental fibrosis and induces regression of established fibrosis. Arthritis Rheum. 63(5), 1396–1404 (2011).
  • Ozgen M, Koca SS, Dagli AF, Gundogdu B, Ustundag B, Isik A. Mycophenolate mofetil and daclizumab targeting T lymphocytes in bleomycin-induced experimental scleroderma. Clin. Exp. Dermatol. 37(1), 48–54 (2012).
  • Koca SS, Ozgen M, Dagli F et al. Proteasome inhibition prevents development of experimental dermal fibrosis. Inflammation 35(3), 810–817 (2011).

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