Epithelial cells undergoing epithelial mesenchymal transition (EMT) in systemic sclerosis lack caveolin-1 and modulate WNT signaling in the dermis by secreting SFRP4

Background Systemic sclerosis is a chronic fibrotic disease highly heterogeneous in clinical outcome, involving autoimmune activation, fibroproliferative vasculopathy and tissue fibrosis of skin and multiple internal organs. The mechanisms linking immune activation and tissue fibrosis are still not fully characterised. A widely accepted model of immune-mediated skin fibrosis is chronic sclerodermoid graft versus host disease (Scl-GVHD), a form of chronic GVHD in patients receiving allogenic bone marrow transplant. Histopathologic studies of cGVHD skin biopsies confirmed the presence of both fibroproliferative vasculopathy and tissue fibrosis in Scl-GVHD. Objective To identify which genes are differentially expressed in SSc skin biopsies are similarly expressed in the transcriptome of Scl-GVHD skin biopsies and therefore of potential importance in linking immune activation and skin fibrosis. Methods Metanalysis of microarray data published in the literature identified a set of 80 genes whose differential expression is highly reproduced in our SSc skin biopsies signature. The mRNA expression level of these genes was then analysed in eight Scl-GVHD and three cGVHD skin biopsies, and compared to normal skin and their differential expression in SSc. Genes found to be significantly differentially expressed (p