Possible strategies for anti-fibrotic drug intervention in scleroderma

Andrew Leask1
1Division of Oral Biology, Department of Dentistry, Schulich School of Medicine and Dentistry, University of Western Ontario, London, Canada

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Akhmetshina A, Dees C, Pileckyte M, Maurer B, Axmann R, Jüngel A, Zwerina J, Gay S, Schett G, Distler O, Distler JH (2008) Dual inhibition of c-abl and PDGF receptor signaling by dasatinib and nilotinib for the treatment of dermal fibrosis. FASEB J 22:2214–2222

Bianco P, Robey PG, Saggio I, Riminucci M (2010) “Mesenchymal” stem cells in human bone marrow (skeletal stem cells): a critical discussion of their nature, identity, and significance in incurable skeletal disease. Hum Gene Ther 21:1057–1066

Bonner JC (2004) Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev 15:255–273

Burgess HA, Daugherty LE, Thatcher TH, Lakatos HF, Ray DM, Redonnet M et al (2005) PPARγ agonists inhibit TGF-β induced pulmonary myofibroblasts differentiation and collagen production: implications for therapy of lung fibrosis. Am J Physiol Lung Cell Mol Physiol 288:L1146–L1153

Chen Y, Abraham DJ, Shi-Wen X, Pearson JD, Black CM, Lyons KM, Leask A (2004) CCN2 (connective tissue growth factor) promotes fibroblast adhesion to fibronectin. Mol Biol Cell 15:5635–5646

Chen Y, Shiwen X, van Beek J, Kennedy L, McLeod M, Renzoni EA, Bou-Gharios G, Wilcox-Adelman S, Goetinck PF, Eastwood M, Black CM, Abraham DJ, Leask A (2005) Matrix contraction by dermal fibroblasts requires TGFbeta/ALK5, heparan sulfate containing proteoglycans and MEK/ERK: insights into pathological scarring in chronic fibrotic disease Am. J Pathol 167:1699–1711

Chen Y, Shi-wen X, Eastwood M, Black CM, Denton CP, Leask A, Abraham DJ (2006) Contribution of activin receptor-like kinase 5 (transforming growth factor beta receptor type I) signaling to the fibrotic phenotype of scleroderma fibroblasts. Arthritis Rheum 54(4):1309–1316

Clozel M, Salloukh H (2005) Role of endothelin in fibrosis and anti-fibrotic potential of bosentan. Ann Med 37:2–12

Denton CP, Black CM, Abraham DJ (2006) Mechanisms and consequences of fibrosis in systemic sclerosis. Nat Clin Pract Rheumatol 2:134–144

Denton CP, Merkel PA, Furst DE, Khanna D, Emery P, Hsu VM, Silliman N, Streisand J, Powell J, Akesson A, Coppock J, Hoogen F, Herrick A, Mayes MD, Veale D, Haas J, Ledbetter S, Korn JH, Black CM, Seibold JR, Cat-192 Study Group, Scleroderma Clinical Trials Consortium (2007) 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 Rheum 56:323–333

Denton CP, Pope JE, Peter HH, Gabrielli A, Boonstra A, van den Hoogen FH, Riemekasten G, De Vita S, Morganti A, Dölberg M, Berkani O, Guillevin L, TRacleer Use in PAH associated with Scleroderma and Connective Tissue Diseases (TRUST) Investigators (2008) Long-term effects of bosentan on quality of life, survival, safety and tolerability in pulmonary arterial hypertension related to connective tissue diseases. Ann Rheum Dis 67:1222–1228

Gabbiani G (2003) The myofibroblast in wound healing and fibrocontractive diseases. J Pathol 200:500–503

Ghosh AK, Varga J (2007) The transcriptional coactivator and acetyltransferase p300 in fibroblast biology and fibrosis. J Cell Physiol 213:663–671

Ghosh AK, Bhattacharyya S, Wei J, Kim S, Barak Y, Mori Y, Varga J (2009) Peroxisome proliferator-activated receptor-gamma abrogates Smad-dependent collagen stimulation by targeting the p300 transcriptional coactivator. FASEB J 23:2968–2977

Grotendorst GR (1997) Connective tissue growth factor: a mediator of TGF-beta action on fibroblasts. Cytokine Growth Factor Rev 8:171–179

Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G (2007) The myofibroblast: one function, multiple origins. Am J Pathol 170:1807–1816

Holmes A, Abraham DJ, Sa S, Shiwen X, Black CM, Leask A (2001) CTGF and SMADs, maintenance of scleroderma phenotype is independent of SMAD signaling. J Biol Chem 276:10594–10601

Ishida W, Mori Y, Lakos G, Sun L, Shan F, Bowes S, Josiah S, Lee WC, Singh J, Ling LE, Varga J (2006) Intracellular TGF-beta receptor blockade abrogates Smad-dependent fibroblast activation in vitro and in vivo. J Invest Dermatol 126:1733–1744

Kapoor M, McCann M, Liu S, Huh K, Denton CP, Abraham DJ, Leask A (2009) Loss of peroxisome proliferator-activated receptor gamma in mouse fibroblasts results in increased susceptibility to bleomycin-induced skin fibrosis. Arthritis Rheum 60:2822–2829

Korn JH, Mayes M, Matucci Cerinic M, Rainisio M, Pope J, Hachulla E, Rich E, Carpentier P, Molitor J, Seibold JR, Hsu V, Guillevin L, Chatterjee S, Peter HH, Coppock J, Herrick A, Merkel PA, Simms R, Denton CP, Furst D, Nguyen N, Gaitonde M, Black C (2004) Digital ulcers in systemic sclerosis: prevention by treatment with bosentan, an oral endothelin receptor antagonist. Arthritis Rheum 50:3985–3993

Kuhn A, Haust M, Ruland V, Weber R, Verde P, Felder G, Ohmann C, Gensch K, Ruzicka T (2010) Effect of bosentan on skin fibrosis in patients with systemic sclerosis: a prospective, open-label, non-comparative trial. Rheumatol Oxford 49:1336–1345

Leask A (2008) Targeting the TGFβ, endothelin-1 and CCN2 axis to combat fibrosis in scleroderma. Cell Signal 20:1409–1414

Leask A (2009) Yin and Yang: CCN3 inhibits the pro-fibrotic effects of CCN2. J Cell Commun Signal 3:161–162

Leask A, Abraham DJ (2004) TGF-beta signaling and the fibrotic response. FASEB J 18:816–827

Leask A, Abraham DJ, Finlay DR, Holmes A, Pennington D, Shi-Wen X, Chen Y, Venstrom K, Dou X, Ponticos M, Black C, Bernabeu C, Jackman JK, Findell PR, Connolly MK (2002) Dysregulation of transforming growth factor beta signaling in scleroderma: overexpression of endoglin in cutaneous scleroderma fibroblasts. Arthritis Rheum 46:1857–1865

Leask A, Holmes A, Black CM, Abraham DJ (2003) Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in fibroblasts. J Biol Chem 278:13008–13015

Leask A, Parapuram SK, Shi-Wen X, Abraham DJ (2009) Connective tissue growth factor (CTGF, CCN2) gene regulation: a potent clinical bio-marker of fibroproliferative disease? J Cell Commun Signal 3:89–94

Liu S, Shi-wen X, Kennedy L, Pala D, Carter DE, Black CM, Abraham DJ, Leask A (2007) FAK is required for TGFβ-induced JNK phosphorylation in fibroblasts: implications for acquisition of a matrix remodeling phenotype. Mol Biol Cell 18:2169–2178

Liu S, Kapoor M, Denton CP, Abraham DJ, Leask A (2009) Loss of β1 integrin in mouse fibroblasts results in resistance to a mouse model of skin scleroderma. Arthritis Rheum 60:2817–2821

Liu S, Taghavi R, Leask A (2010) Connective tissue growth factor is induced in bleomycin-induced skin scleroderma. J Cell Commun Signal 4:25–30

Liu S, Shi-Wen X, Abraham DJ, Leask A (2011) CCN2 is required for bleomycin-induced skin fibrosis. Arthritis Rheum 63:239–246

Mori T, Kawara S, Shinozaki M, Hayashi N, Kakinuma T, Igarashi A, Takigawa M, Nakanishi T, Takehara K (1999) Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: a mouse fibrosis model. J Cell Physiol 181:153–159

Mori Y, Hinchcliff M, Wu M, Warner-Blankenship M, Lyons K, Varga J (2008) Connective tissue growth factor/CCN2-null mouse embryonic fibroblasts retain intact transforming growth factor-beta responsiveness. Exp Cell Res 314:1094–1104

Moussad EE, Brigstock DR (2000) Connective tissue growth factor: what’s in a name? Mol Genet Metab 71:276–292

Pannu J, Nakerakanti S, Smith E, ten Dijke P, Trojanowska M (2007) Transforming growth factor-beta receptor type I-dependent fibrogenic gene program is mediated via activation of Smad1 and ERK1/2 pathways. J Biol Chem 282:10405–10413

Park SH, Saleh D, Giaid A, Michel RP (1997) Increased endothelin-1 in bleomycin-induced pulmonary fibrosis and the effect of an endothelin receptor antagonist. Am J Respir Crit Care Med 156(2 Pt 1):600–608

Ponticos M, Holmes AM, Shiwen X, Pl L, Khan K, Rajkumar VS, Hoyles RK, Bou-Gharios G, Black CM, Denton CP, Abraham DJ, Leask A, Lindahl GE (2009) Pivotal role of connective tissue growth factor in lung fibrosis: MAPK-dependent transcriptional activation of type I collagen. Arthritis Rheum 60:2142–2155

Rajkumar VS, Sundberg C, Abraham DJ, Rubin K, Black CM (1999) Activation of microvascular pericytes in autoimmune Raynaud’s phenomenon and systemic sclerosis. Arthritis Rheum 42:930–941

Rajkumar VS, Shiwen X, Bostrom M, Leoni P, Muddle J, Ivarsson M, Gerdin B, Denton CP, Bou-Gharios G, Black CM, Abraham DJ (2006) Platelet-derived growth factor-beta receptor activation is essential for fibroblast and pericyte recruitment during cutaneous wound healing. Am J Pathol 169:2254–2265

Riser BL, Najmabadi F, Perbal B, Peterson DR, Rambow JA, Riser ML, Sukowski E, Yeger H, Riser SC (2009) CCN3 (NOV) is a negative regulator of CCN2 (CTGF) and a novel endogenous inhibitor of the fibrotic pathway in an in vitro model of renal disease. Am J Pathol 174:1725–1734

Santander C, Brandan E (2006) Betaglycan induces TGF-beta signaling in a ligand-independent manner, through activation of the p38 pathway. Cell Signal 18:1482–1491

Seibold JR, Denton CP, Furst DE, Guillevin L, Rubin LJ, Wells A, Matucci Cerinic M, Riemekasten G, Emery P, Chadha-Boreham H, Charef P, Roux S, Black CM (2010) Randomized, prospective, placebo-controlled trial of bosentan in interstitial lung disease secondary to systemic sclerosis. Arthritis Rheum 62:2101–2108

Shi-Wen X, Chen Y, Denton CP, Eastwood M, Renzoni EA, Bou-Gharios G, Pearson JD, Dashwood M, du Bois RM, Black CM, Leask A, Abraham DJ (2004) 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 15:2707–2719

Shi-wen X, Howat SL, Renzoni EA, Holmes A, Pearson JD, Dashwood MR, Bou-Gharios G, Denton CP, du Bois RM, Black CM, Leask A, Abraham DJ (2004) Endothelin-1 induces expression of matrix-associated genes in lung fibroblasts through MEK/ERK. J Biol Chem 279:23098–23103

Shi-wen X, Rodrigues-Pascual F, Lamas S, Holmes A, Howat S, Pearson JD, Dashwood MR, du Bois RM, Denton CP, Black CM, Abraham DJ, Leask A (2006a) Constitutive ALK5-indepenent JNK activation contributes to endothelin-1 over-expression in pulmonary fibrosis. Mol Cell Biol 26:5518–5527

Shi-wen X, Stanton L, Kennedy L, Pala D, Chen Y, Howat SL, Renzoni EA, Carter DE, Bou-Gharios G, Stratton RJ, Pearson JD, Beier F, Lyons KM, Black CM, Abraham DJ, Leask A (2006b) CCN2 is necessary for adhesive responses to TGFß1 in embryonic fibroblasts. J Biol Chem 281:10715–10726

Shi-wen X, Renzoni EA, Kennedy L, Howat S, Chen Y, Pearson JD, Bou-Gharios G, Dashwood MR, du Bois RM, Black CM, Denton CP, Abraham DJ, Leask A (2007) Endogenous endothelin-1 signaling contributes to type I collagen and CCN2 overexpression in fibrotic fibroblasts. Matrix Biol 26:625–632

Sime PJ (2008) The antifibrogenic potential of PPARgamma ligands in pulmonary fibrosis. J Investig Med 56:534–538

Wu M, Melichian DS, Chang E, Warner-Blankenship M, Ghosh AK, Varga J (2009) Rosiglitazone abrogates bleomycin-induced scleroderma and blocks profibrotic responses through peroxisome proliferator-activated receptor-gamma. Am J Pathol 174:519–533

Yeger H, Perbal B (2007) The CCN family of genes: a perspective on CCN biology and therapeutic potential. J Cell Commun Signal 1:159–164

Yoon PO, Lee MA, Cha H, Jeong MH, Kim J, Jang SP, Choi BY, Jeong D, Yang DK, Hajjar RJ, Park WJ (2010) The opposing effects of CCN2 and CCN5 on the development of cardiac hypertrophy and fibrosis. J Mol Cell Cardiol 49:294–303