Abstract
Scleroderma, an autoimmune disorder characterized by skin and organ fibrosis, has no treatment. Although over the past decade valuable insights into the molecular mechanisms underlying scleroderma have been generated, results in clinical trials have been disappointing. This issue is likely to arise due to the heterogeneity of scleroderma. Molecular insights into the heterogeneity of this disease have been provided by genome-wide expression profiling. In a recent paper, Bhattacharyya and colleagues (PLOS One 6:e23082, 2011b) to show that the overexpression of a range of "fibroproliferative" genes in diffuse cutaneous scleroderma patients are likely to be caused by the overexpression of transcription factor Early growth response (Egr)-1. Only a minority of Egr-1-regulated genes were also found to be regulated by TGF-ß. Moreover, Greenblatt and colleagues (Am J Pathol., 2012) have shown that the overexpression of "inflammatory" genes overexpressed in "localized" scleroderma and a small subset of limited and diffuse scleroderma patients is likely to be due to the activity of interleukin-13 (IL-13). Intriguingly, at a gene expression level, murine sclerodermatous graft-versus-host disease (sclGVHD) approximates this inflammatory sub...Continue Reading
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