Emerging targeted therapies in scleroderma lung and skin fibrosis

Best Practice and Research: Clinical Rheumatology

Volumn 25, Issue 6, 2011, Pages 843-858

  Maurer, Britta ^a   Distler, Oliver ^a  

^a UNIVERSITY HOSPITAL ZURICH   (Switzerland)

Author keywords

Interstitial lung disease; Skin fibrosis; SSc; Targeted anti fibrotic therapies

Indexed keywords

2,3 DIHYDRO 2 OXO 3 (4,5,6,7 TETRAHYDRO 1H INDOL 2 YLMETHYLENE) 1H INDOLE 5 SULFONIC ACID DIMETHYLAMIDE; 5 AZA 2' DEOXYCYTIDINE; BOSENTAN; CALVASCULIN; CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CXCR4; CONNECTIVE TISSUE GROWTH FACTOR; DASATINIB; ENDOTHELIN 1; IMATINIB; INTERLEUKIN 13; INTERLEUKIN 13 ANTIBODY; INTERLEUKIN 6; METELIMUMAB; MONOCYTE CHEMOTACTIC PROTEIN 1; NILOTINIB; NOTCH RECEPTOR; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PLERIXAFOR; PROSTAGLANDIN J2; ROSIGLITAZONE; SAR 100842; STAT4 PROTEIN; STROMAL CELL DERIVED FACTOR 1; TOCILIZUMAB; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR FRA 2; TRANSFORMING GROWTH FACTOR BETA; TRICHOSTATIN A; UNCLASSIFIED DRUG; WNT PROTEIN;

CREATINE KINASE BLOOD LEVEL; DRUG EFFECT; DRUG MECHANISM; DRUG TARGETING; EDEMA; FIBROSING ALVEOLITIS; GENETIC SUSCEPTIBILITY; HUMAN; INTERSTITIAL LUNG DISEASE; LUNG FIBROSIS; MYALGIA; NAUSEA; NONHUMAN; PRIORITY JOURNAL; PROTEIN FUNCTION; REVIEW; SCLERODERMA; SIDE EFFECT; SKIN FIBROSIS; SYSTEMIC SCLEROSIS;

FIBROSIS; FORECASTING; HUMANS; LUNG DISEASES, INTERSTITIAL; SCLERODERMA, SYSTEMIC; SKIN; THERAPIES, INVESTIGATIONAL;

EID: 84855995748     PISSN: 15216942     EISSN: 15321770     Source Type: Journal    
DOI: 10.1016/j.berh.2011.11.007     Document Type: Review

References (88)

1. J. Varga, and D. Abraham Systemic sclerosis: a prototypic multisystem fibrotic disorder Journal of Clinical Investigation 117 2007 557 567 (Pubitemid 46348510)
2. V.D. Steen, and T.A. Medsger Changes in causes of death in systemic sclerosis, 1972-2002 Annals of the Rheumatic Diseases 66 2007 940 944 (Pubitemid 46999798)
3. F.C. Arnett, M. Cho, S. Chatterjee, M.B. Aguilar, J.D. Reveille, and M.D. Mayes Familial occurrence frequencies and relative risks for systemic sclerosis (scleroderma) in three United States cohorts Arthritis & Rheumatism 44 2001 1359 1362 (Pubitemid 32537534)
4. T. Frech, D. Khanna, B. Markewitz, G. Mineau, R. Pimentel, and A. Sawitzke Heritability of vasculopathy, autoimmune disease, and fibrosis in systemic sclerosis: a population-based study Arthritis & Rheumatism 62 2010 2109 2116
5. T.R. Radstake, O. Gorlova, B. Rueda, J.E. Martin, B.Z. Alizadeh, and R. Palomino-Morales Genome-wide association study of systemic sclerosis identifies CD247 as a new susceptibility locus Nature Genetics 42 2010 426 429
6. Y.S.M. Allanore, P. Dieudé, J. Avouac, J. Distler, C. Boileau, and M. Martinez European GENESIS Consortium. Genomwide scan identifies TNIP1, PSORS1C1 and RHOB as novel risk loci for systemic sclerosis Annals of the Rheumatic Diseases 70 Suppl. 3 2011 148
7. O. Gorlova, J.E. Martin, B. Rueda, B.P. Koeleman, J. Ying, and M. Teruel Identification of novel genetic markers associated with clinical phenotypes of systemic sclerosis through a genome-wide association strategy PLoS Genetics 7 2011 e1002178
8. S.K. Agarwal, and J.D. Reveille The genetics of scleroderma (systemic sclerosis) Current Opinion in Rheumatology 22 2010 133 138
9. T. Warchol, P. Piotrowski, M. Lianeri, D. Cieslak, M. Wudarski, and P. Hrycaj The CD3Z 844 T > A polymorphism within the 3'-UTR of CD3Z confers increased risk of incidence of systemic lupus erythematosus Tissue Antigens 74 2009 68 72
10. Y. Wang, P.S. Fan, and B. Kahaleh Association between enhanced type I collagen expression and epigenetic repression of the FLI1 gene in scleroderma fibroblasts Arthritis & Rheumatism 54 2006 2271 2279 (Pubitemid 44051084)
11. L.C. Huber, J.H. Distler, F. Moritz, H. Hemmatazad, T. Hauser, and B.A. Michel Trichostatin A prevents the accumulation of extracellular matrix in a mouse model of bleomycin-induced skin fibrosis Arthritis & Rheumatism 56 2007 2755 2764 (Pubitemid 47237295)
12. C.A.A. Dees, N. Busch, A. Horn, J. Gusinde, A. Jüngel, and S. Gay TGFb stimulates promoter hypermethylation and subsequent silencing of the anti-fibrotic gene socs-3 Arthritis & Rheumatism 2009 (Suppl. 10)
13. K. Rombouts, T. Niki, A. Wielant, K. Hellemans, A. Geerts, and A. Trichostatin Lead compound for development of antifibrogenic drugs Acta Gastroenterology Belgium 64 2001 239 246 (Pubitemid 32953886)
14. M. Pang, and S. Zhuang Histone deacetylase: a potential therapeutic target for fibrotic disorders Journal of Pharmacology and Experimental Therapeutics 335 2010 266 272
15. J. Elmen, M. Lindow, S. Schutz, M. Lawrence, A. Petri, and S. Obad LNA-mediated microRNA silencing in non-human primates Nature 452 2008 896 899 (Pubitemid 351550859)
16. B. Maurer, J. Stanczyk, A. Jungel, A. Akhmetshina, M. Trenkmann, and M. Brock MicroRNA-29, a key regulator of collagen expression in systemic sclerosis Arthritis & Rheumatism 62 2010 1733 1743
17. J. Avouac, B.G. Furnrohr, M. Tomcik, K. Palumbo, P. Zerr, and A. Horn Inactivation of the transcription factor STAT-4 prevents inflammation-driven fibrosis in animal models of systemic sclerosis Arthritis & Rheumatism 63 2011 800 809
18. N. Nath, S. Giri, R. Prasad, A.K. Singh, and I. Singh Potential targets of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor for multiple sclerosis therapy Journal of Immunology 172 2004 1273 1286 (Pubitemid 38113791)
19. G. Lakos, D. Melichian, M. Wu, and J. Varga Increased bleomycin-induced skin fibrosis in mice lacking the Th1-specific transcription factor T-bet Pathobiology 73 2006 224 237 (Pubitemid 46332830)
20. R. Eferl, P. Hasselblatt, M. Rath, H. Popper, R. Zenz, and V. Komnenovic Development of pulmonary fibrosis through a pathway involving the transcription factor Fra-2/AP-1 Proceedings of the National Academy of Sciences of the Unites States of America 105 2008 10525 10530
21. N. Reich, B. Maurer, A. Akhmetshina, P. Venalis, C. Dees, and P. Zerr The transcription factor Fra-2 regulates the production of extracellular matrix in systemic sclerosis Arthritis & Rheumatism 62 2010 280 290
22. B. Maurer, N. Busch, A. Jungel, M. Pileckyte, R.E. Gay, and B.A. Michel Transcription factor fos-related antigen-2 induces progressive peripheral vasculopathy in mice closely resembling human systemic sclerosis Circulation 120 2009 2367 2376
23. B. Maurer, A. Jüngel, R.E. Gay, G. Schett, B.A. Michel, and S. Gay Fra-2 transgenic mice as a novel model for the pulmonary vasculopathy and pulmonary fibrosis of SSc Annals of the Rheumatic Diseases 69 Suppl. 3 2010 409
24. K.Z.P. Palumbo, M. Tomcik, A. Horn, S. Vollath, C. Dees, and A. Akhmetshina The transcription factor JunD mediates transforming growth factor-beta induced fibroblast activation and fibrosis in systemic sclerosis Annals of the Rheumatic Diseases 70 Suppl. 3 2011 488
25. K. Tsuchida, H. Chaki, T. Takakura, J. Yokotani, Y. Aikawa, and S. Shiozawa Design, synthesis, and biological evaluation of new cyclic disulfide decapeptides that inhibit the binding of AP-1 to DNA Journal of Medicinal Chemistry 47 2004 4239 4246 (Pubitemid 39045429)
26. J.P.K. Avouac, M. Tomcik, P. Zerr, S. Shiozawa, O. Distler, and G. Schett Inhibition of AP-1 signaling abrogates TGF-beta mediated activation of fibroblasts and prevents experimental fibrosis Annals of the Rheumatic Diseases 70 Suppl3 2011 533
27. A.K. Ghosh, S. Bhattacharyya, J. Wei, S. Kim, Y. Barak, and Y. Mori Peroxisome proliferator-activated receptor-gamma abrogates Smad-dependent collagen stimulation by targeting the p300 transcriptional coactivator FASEB Journal 23 2009 2968 2977
28. J. Wei, A.K. Ghosh, J.L. Sargent, K. Komura, M. Wu, and Q.Q. Huang PPARgamma downregulation by TGFss in fibroblast and impaired expression and function in systemic sclerosis: a novel mechanism for progressive fibrogenesis PLoS One 5 2010 e13778
29. M. Wu, D.S. Melichian, E. Chang, M. Warner-Blankenship, A.K. Ghosh, and J. Varga Rosiglitazone abrogates bleomycin-induced scleroderma and blocks profibrotic responses through peroxisome proliferator-activated receptor-gamma American Journal of Pathology 174 2009 519 533
30. G.Y. Jin, S.M. Bok, Y.M. Han, M.J. Chung, K.H. Yoon, and S.R. Kim Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: assessed by micro-computed tomography and pathologic scores European Journal of Radiology 2011 [Epub ahead of print]
31. M.P.K. Tomcik, P. Zerr, B.G. Fuernrohr, J. Avouac, A. Horn, and C. Dees S100A4 mediates the profibrotic effects of TGF-beta in dermal fibrosis in systemic sclerosis Annals of the Rheumatic Diseases 70 Suppl. 3 2011 492
32. C. Dees, M. Tomcik, P. Zerr, A. Akhmetshina, A. Horn, and K. Palumbo Notch signalling regulates fibroblast activation and collagen release in systemic sclerosis Annals of the Rheumatic Diseases 70 2011 1304 1310
33. C. Dees, P. Zerr, M. Tomcik, C. Beyer, A. Horn, and A. Akhmetshina Inhibition of Notch signaling prevents experimental fibrosis and induces regression of established fibrosis Arthritis & Rheumatism 63 2011 1396 1404
34. R.K. Hoyles, E.C. Derrett-Smith, K. Khan, X. Shiwen, S.L. Howat, and A.U. Wells An essential role for resident fibroblasts in experimental lung fibrosis is defined by lineage-specific deletion of high-affinity type II transforming growth factor beta receptor American Journal of Respiratory and Critical Care Medicine 183 2011 249 261
35. M. Hasegawa, Y. Matsushita, M. Horikawa, K. Higashi, Y. Tomigahara, and H. Kaneko A novel inhibitor of Smad-dependent transcriptional activation suppresses tissue fibrosis in mouse models of systemic sclerosis Arthritis & Rheumatism 60 2009 3465 3475
36. L. Arribillaga, J. Dotor, M. Basagoiti, J.I. Riezu-Boj, F. Borras-Cuesta, and J.J. Lasarte Therapeutic effect of a peptide inhibitor of TGF-beta on pulmonary fibrosis Cytokine 53 2011 327 333
37. C.P. Denton, P.A. Merkel, D.E. Furst, D. Khanna, P. Emery, and V.M. Hsu Recombinant human anti-transforming growth factor beta1 antibody therapy in systemic sclerosis: a multicenter, randomized, placebo-controlled phase I/II trial of CAT-192 Arthritis & Rheumatism 56 2007 323 333 (Pubitemid 46106206)
38. A. Akhmetshina, P. Venalis, C. Dees, N. Busch, J. Zwerina, and G. Schett Treatment with imatinib prevents fibrosis in different preclinical models of systemic sclerosis and induces regression of established fibrosis Arthritis & Rheumatism 60 2009 219 224
39. J.H. Distler, A. Jungel, L.C. Huber, U. Schulze-Horsel, J. Zwerina, and R.E. Gay Imatinib mesylate reduces production of extracellular matrix and prevents development of experimental dermal fibrosis Arthritis & Rheumatism 56 2007 311 322 (Pubitemid 46106205)
40. N. Iwamoto, J.H. Distler, and O. Distler Tyrosine kinase inhibitors in the treatment of systemic sclerosis: from animal models to clinical trials Current Rheumatology Reports 13 2011 21 27
41. A. Akhmetshina, C. Dees, M. Pileckyte, B. Maurer, R. Axmann, and A. Jungel Dual inhibition of c-abl and PDGF receptor signaling by dasatinib and nilotinib for the treatment of dermal fibrosis FASEB Journal 22 2008 2214 2222 (Pubitemid 351948641)
42. B. Maurer, A. Jüngel, R.E. Gay, G. Schett, B.A. Michel, and S. Gay Tyrosine kinase inhibitors (TKI) war promising therapeutic agents for the proliferative vasculopathy in SSc Arthritis & Rheumatism 60 Suppl. 10 2009 1263
43. C. Skhirtladze, O. Distler, C. Dees, A. Akhmetshina, N. Busch, and P. Venalis Src kinases in systemic sclerosis: central roles in fibroblast activation and in skin fibrosis Arthritis & Rheumatism 58 2008 1475 1484 (Pubitemid 351705937)
44. D. Abraham Connective tissue growth factor: growth factor, matricellular organizer, fibrotic biomarker or molecular target for anti-fibrotic therapy in SSc? Rheumatology 47 Suppl. 5 2008 v8 v9
45. X. Shi-Wen, L. Kennedy, E.A. Renzoni, G. Bou-Gharios, R.M. du Bois, and C.M. Black Endothelin is a downstream mediator of profibrotic responses to transforming growth factor beta in human lung fibroblasts Arthritis & Rheumatism 56 2007 4189 4194 (Pubitemid 350262347)
46. S.H. Park, D. Saleh, A. Giaid, and R.P. Michel Increased endothelin-1 in bleomycin-induced pulmonary fibrosis and the effect of an endothelin receptor antagonist American Journal of Respiratory and Critical Care Medicine 156 1997 600 608 (Pubitemid 27352001)
47. J.R. Seibold, C.P. Denton, D.E. Furst, L. Guillevin, L.J. Rubin, and A. Wells Randomized, prospective, placebo-controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis Arthritis & Rheumatism 62 2010 2101 2108
48. T.E. King Jr., J. Behr, K.K. Brown, R.M. du Bois, L. Lancaster, and J.A. de Andrade BUILD-1: a randomized placebo-controlled trial of bosentan in idiopathic pulmonary fibrosis American Journal of Respiratory and Critical Care Medicine 177 2008 75 81
49. T.E. King Jr., K.K. Brown, G. Raghu, R.M. du Bois, D.A. Lynch, and F. Martinez BUILD-3: a randomized, controlled trial of bosentan in idiopathic pulmonary fibrosis American Journal of Respiratory and Critical Care Medicine 184 1 2011 92 99
50. A. Kuhn, M. Haust, V. Ruland, R. Weber, P. Verde, and G. Felder Effect of bosentan on skin fibrosis in patients with systemic sclerosis: a prospective, open-label, non-comparative trial Rheumatology 49 2010 1336 1345
51. P. Fuschiotti, T.A. Medsger Jr., and P.A. Morel Effector CD8+ T cells in systemic sclerosis patients produce abnormally high levels of interleukin-13 associated with increased skin fibrosis Arthritis & Rheumatism 60 2009 1119 1128
52. A. Hancock, L. Armstrong, R. Gama, and A. Millar Production of interleukin 13 by alveolar macrophages from normal and fibrotic lung American Journal of Respiratory Cell and Molecular Biology 18 1 1998 Jan 60 65 (Pubitemid 128355347)
53. S. Fichtner-Feigl, W. Strober, K. Kawakami, R.K. Puri, and A. Kitani IL-13 signaling through the IL-13alpha2 receptor is involved in induction of TGF-beta1 production and fibrosis Nature Medicine 12 2006 99 106 (Pubitemid 43050083)
54. S. Sato, M. Hasegawa, and K. Takehara Serum levels of interleukin-6 and interleukin-10 correlate with total skin thickness score in patients with systemic sclerosis Journal of Dermatological Science 27 2001 140 146 (Pubitemid 32781022)
55. F. Saito, S. Tasaka, K. Inoue, K. Miyamoto, Y. Nakano, and Y. Ogawa Role of interleukin-6 in bleomycin-induced lung inflammatory changes in mice American Journal of Respiratory Cell and Molecular Biology 38 2008 566 571 (Pubitemid 351758675)
56. Y. Shima, Y. Kuwahara, H. Murota, S. Kitaba, M. Kawai, and T. Hirano The skin of patients with systemic sclerosis softened during the treatment with anti-IL-6 receptor antibody tocilizumab Rheumatology 49 2010 2408 2412
57. M.M.-C.M. Meunier, B. Maurer, G. Riemekasten, F. Bartoli, G. Fiori, and O. Distler Outcomes of systemic sclerosis associated polyarthritis patients treated by biotherapies tocilizumab or abatacept: a EUSTAR observational study Annals of the Rheumatic Diseases 70 Suppl. 3 2011 660
58. P. Cipriani, A. Franca Milia, V. Liakouli, A. Pacini, M. Manetti, and A. Marrelli Differential expression of stromal cell-derived factor 1 and its receptor CXCR4 in the skin and endothelial cells of systemic sclerosis patients: Pathogenetic implications Arthritis & Rheumatism 54 2006 3022 3033 (Pubitemid 44497784)
59. P. Cipriani, S. Guiducci, I. Miniati, M. Cinelli, S. Urbani, and A. Marrelli Impairment of endothelial cell differentiation from bone marrow-derived mesenchymal stem cells: new insight into the pathogenesis of systemic sclerosis Arthritis & Rheumatism 56 2007 1994 2004 (Pubitemid 47110398)
60. R.J. Phillips, M.D. Burdick, K. Hong, M.A. Lutz, L.A. Murray, and Y.Y. Xue Circulating fibrocytes traffic to the lungs in response to CXCL12 and mediate fibrosis Journal of Clinical Investigation 114 2004 438 446 (Pubitemid 39071616)
61. J.S. Song, C.M. Kang, H.H. Kang, H.K. Yoon, Y.K. Kim, and K.H. Kim Inhibitory effect of CXC chemokine receptor 4 antagonist AMD3100 on bleomycin induced murine pulmonary fibrosis Experimental and Molecular Medicine 42 2010 465 472
62. J.H. Distler, A. Akhmetshina, G. Schett, and O. Distler Monocyte chemoattractant proteins in the pathogenesis of systemic sclerosis Rheumatology 48 2009 98 103
63. A.M. Tager, P. LaCamera, B.S. Shea, G.S. Campanella, M. Selman, and Z. Zhao The lysophosphatidic acid receptor LPA1 links pulmonary fibrosis to lung injury by mediating fibroblast recruitment and vascular leak Nature Medicine 14 2008 45 54
64. J.S. Swaney, C. Chapman, L.D. Correa, K.J. Stebbins, R.A. Bundey, and P.C. Prodanovich A novel, orally active LPA(1) receptor antagonist inhibits lung fibrosis in the mouse bleomycin model British Journal of Pharmacology 160 2010 1699 1713
65. A. Tokumura, L.D. Carbone, Y. Yoshioka, J. Morishige, M. Kikuchi, and A. Postlethwaite Elevated serum levels of arachidonoyl-lysophosphatidic acid and sphingosine 1-phosphate in systemic sclerosis International Journal of Medical Sciences 6 2009 168 176
66. F.V. Castelino, J. Seiders, G. Bain, S.F. Brooks, C.D. King, and J.S. Swaney Amelioration of dermal fibrosis by genetic deletion or pharmacologic antagonism of lysophosphatidic acid receptor 1 in a mouse model of scleroderma Arthritis & Rheumatism 63 2011 1405 1415
67. M. Konigshoff, M. Kramer, N. Balsara, J. Wilhelm, O.V. Amarie, and A. Jahn WNT1-inducible signaling protein-1 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis Journal of Clinical Investigation 119 2009 772 787
68. J. Bayle, J. Fitch, K. Jacobsen, R. Kumar, R. Lafyatis, and R. Lemaire Increased expression of Wnt2 and SFRP4 in Tsk mouse skin: role of Wnt signaling in altered dermal fibrillin deposition and systemic sclerosis Journal of Investigative Dermatology 128 2008 871 881 (Pubitemid 351374297)
69. J. Wei, D. Melichian, K. Komura, M. Hinchcliff, A.P. Lam, and R. Lafyatis Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: a novel mouse model for scleroderma? Arthritis & Rheumatism 63 2011 1707 1717
70. A.P. Lam, A.S. Flozak, S. Russell, J. Wei, M. Jain, and G.M. Mutlu Nuclear {beta}-catenin is increased in SSc pulmonary fibrosis and promotes lung fibroblast migration and proliferation American Journal of Respiratory Cell and Molecular Biology 45 5 2011 915 922
71. A. Yoshizaki, K. Yanaba, Y. Iwata, K. Komura, F. Ogawa, and M. Takenaka Treatment with rapamycin prevents fibrosis in tight-skin and bleomycin-induced mouse models of systemic sclerosis Arthritis & Rheumatism 62 2010 2476 2487
72. T.I. Su, D. Khanna, D.E. Furst, G. Danovitch, C. Burger, and P. Maranian Rapamycin versus methotrexate in early diffuse systemic sclerosis: results from a randomized, single-blind pilot study Arthritis & Rheumatism 60 2009 3821 3830
73. T.R. Radstake, L. van Bon, J. Broen, A. Hussiani, R. Hesselstrand, and D.M. Wuttge The pronounced Th17 profile in systemic sclerosis (SSc) together with intracellular expression of TGFbeta and IFNgamma distinguishes SSc phenotypes PLoS One 4 2009 e5903
74. M. Pines, D. Snyder, S. Yarkoni, and A. Nagler Halofuginone to treat fibrosis in chronic graft-versus-host disease and scleroderma Biology of Blood and Marrow Transplantation 9 2003 417 425 (Pubitemid 38351799)
75. M.O. Becker, C. Bruckner, H.U. Scherer, N. Wassermann, J.Y. Humrich, and L.G. Hanitsch The monoclonal anti-CD25 antibody basiliximab for the treatment of progressive systemic sclerosis: an open-label study Annals of the Rheumatic Diseases 70 2011 1340 1341
76. M.L. Whitfield, D.R. Finlay, J.I. Murray, O.G. Troyanskaya, J.T. Chi, and A. Pergamenschikov Systemic and cell type-specific gene expression patterns in scleroderma skin Proceedings of the National Academy of Sciences of the Unites States of America 100 2003 12319 12324 (Pubitemid 37271558)
77. A. Yoshizaki, Y. Iwata, K. Komura, F. Ogawa, T. Hara, and E. Muroi CD19 regulates skin and lung fibrosis via Toll-like receptor signaling in a model of bleomycin-induced scleroderma American Journal of Pathology 172 2008 1650 1663 (Pubitemid 351793356)
78. V. Smith, J.T. Van Praet, B. Vandooren, B. Van der Cruyssen, J.M. Naeyaert, and S. Decuman Rituximab in diffuse cutaneous systemic sclerosis: an open-label clinical and histopathological study Annals of the Rheumatic Diseases 69 2010 193 197
79. A.C.I. Francois, E. Chatelus, Y. Allanore, J. Avouac, B. Ryffel, and A. Davidson Pathogenic profibrotic role of BAFF in patients with systemic sclerosis and in the bleomycin model Annals of the Rheumatic Diseases 70 Suppl. 3 2011 149
80. T. Ohba, J.K. McDonald, R.M. Silver, C. Strange, E.C. LeRoy, and A. Ludwicka Scleroderma bronchoalveolar lavage fluid contains thrombin, a mediator of human lung fibroblast proliferation via induction of platelet-derived growth factor alpha-receptor American Journal of Respiratory Cell and Molecular Biology 10 1994 405 412
81. D.C. Howell, R.H. Johns, J.A. Lasky, B. Shan, C.J. Scotton, and G.J. Laurent Absence of proteinase-activated receptor-1 signaling affords protection from bleomycin-induced lung inflammation and fibrosis American Journal of Pathology 166 2005 1353 1365 (Pubitemid 40586507)
82. G.S. Bogatkevich, A. Ludwicka-Bradley, and R.M. Silver Dabigatran, a direct thrombin inhibitor, demonstrates antifibrotic effects on lung fibroblasts Arthritis & Rheumatism 60 2009 3455 3464
83. C. Dees, A. Akhmetshina, P. Zerr, N. Reich, K. Palumbo, and A. Horn Platelet-derived serotonin links vascular disease and tissue fibrosis Journal of Experimental Medicine 208 2011 961 972
84. S. Amjadi, P. Maranian, D.E. Furst, P.J. Clements, W.K. Wong, and A.E. Postlethwaite Course of the modified Rodnan skin thickness score in systemic sclerosis clinical trials: analysis of three large multicenter, double-blind, randomized controlled trials Arthritis & Rheumatism 60 2009 2490 2498
85. L. Shand, M. Lunt, S. Nihtyanova, M. Hoseini, A. Silman, and C.M. Black Relationship between change in skin score and disease outcome in diffuse cutaneous systemic sclerosis: application of a latent linear trajectory model Arthritis & Rheumatism 56 2007 2422 2431 (Pubitemid 47173590)
86. R.T. Domsic, T. Rodriguez-Reyna, M. Lucas, N. Fertig, and T.A. Medsger Jr. Skin thickness progression rate: a predictor of mortality and early internal organ involvement in diffuse scleroderma Annals of the Rheumatic Diseases 70 2011 104 109
87. D. Khanna, K.K. Brown, P.J. Clements, R. Elashoff, D.E. Furst, and J. Goldin Systemic sclerosis-associated interstitial lung disease-proposed recommendations for future randomized clinical trials Clinical and Experimental Rheumatology 28 2010 S55 S62
88. Q. Wang, W. Usinger, B. Nichols, J. Gray, L. Xu, and T.W. Seeley Cooperative interaction of CTGF and TGF-beta in animal models of fibrotic disease Fibrogenesis Tissue Repair 4 2011 4