Recent studies have highlighted a potentially important role for Wnts as profibrotic mediators, and implicated increased Wnt activity in systemic sclerosis and other fibrotic diseases. Strikingly, new data indicates that Wnts have a central role in the profibrotic activity of TGF-β.
References
Akhmetshina, A. et al. Activation of canonical Wnt signalling is required for TGF-β-mediated fibrosis. Nat. Commun. 3, 735 (2012).
Nishita, M. et al. Interaction between Wnt and TGF-β signalling pathways during formation of Spemann's organizer. Nature 403, 781–785 (2000).
Lemaire, R. et al. Antagonistic effect of the matricellular signaling protein CCN3 on TGF-β- and Wnt-mediated fibrillinogenesis in systemic sclerosis and Marfan syndrome. J. Invest. Dermatol. 130, 1514–1523 (2010).
Wei, J. et al. Canonical Wnt signaling induces skin fibrosis and subcutaneous lipoatrophy: a novel mouse model for scleroderma? Arthritis Rheum. 63, 1707–1717 (2011).
Brack, A. S. et al. Increased Wnt signaling during aging alters muscle stem cell fate and increases fibrosis. Science 317, 807–810 (2007).
Wei, J. et al. Wnt/β-catenin signaling is hyperactivated in systemic sclerois and induces smad-dependent fibrotic responses in mesenchymal cells. Arthritis Rheum. http://dx.doi.org/10.1002/art.34424.
Bayle, J. et al. Increased expression of Wnt2 and SFRP4 in Tsk mouse skin: role of Wnt signaling in altered dermal fibrillin deposition and systemic sclerosis. J. Invest. Dermatol. 128, 871–881 (2008).
van Amerongen, R. & Nusse, R. Towards an integrated view of Wnt signaling in development. Development 136, 3205–3214 (2009).
Lam, A. P. et al. Nuclear beta-catenin is increased in systemic sclerosis pulmonary fibrosis and promotes lung fibroblast migration and proliferation. Am. J. Respir. Cell Mol. Biol. 45, 915–922 (2011).
Farina, G., Lafyatis, D., Lemaire, R. & Lafyatis, R. A four-gene biomarker predicts skin disease in patients with diffuse cutaneous systemic sclerosis. Arthritis Rheum. 62, 580–588 (2010).
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Lafyatis, R. SSc—fibrosis takes flight with Wingless inhibition. Nat Rev Rheumatol 8, 441–442 (2012). https://doi.org/10.1038/nrrheum.2012.99
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DOI: https://doi.org/10.1038/nrrheum.2012.99
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