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Pubmed- S100A4 Expression is Increased in Stricture Fibroblasts From Patients with Fibrostenosing Crohn's Disease and Promotes Intestinal Fibroblast Migration.


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Posted 22 May 2010 - 06:17 AM

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S100A4 Expression is Increased in Stricture Fibroblasts From Patients with Fibrostenosing Crohn's Disease and Promotes Intestinal Fibroblast Migration.

Am J Physiol Gastrointest Liver Physiol. 2010 May 20;

Authors: Cunningham MF, Docherty NG, Burke JP, O'Connell PR

Introduction: Fibroblasts represent the key cell type in fibrostenosing Crohn's Disease (FCD) pathogenesis. S100A4 is an EF-hand calcium binding protein family member, implicated in epithelial-mesenchymal-transition (EMT), and as a marker of activated T-lymphocytes and fibroblasts in chronic tissue remodelling. The aim of this study was to examine the expression profile of S100A4 in the resected ileum of patients with FCD. Materials and Methods: Mucosa, seromuscular explants and transmural biopsies were harvested from diseased and proximal, macroscopically normal margins of ileocaecal resections for FCD. Samples were processed for histochemistry, immunohistochemistry, real-time RT-PCR, Western blotting and transmission electron microscopy. Primary explant cultures of seromuscular fibroblasts were exposed to TGF-beta1 (1ng/ml) and S100A4 expression and scratch wound healing activity assessed at 24 hours. CCD-18 Co fibroblasts were transfected with S100A4 si-RNA, and subsequently treated with TGF-beta1 (1ng/ml) for 30 minutes or 24 hours, then assessed for S100A4 and Smad3 expression and scratch wound healing activity. Results: S100A4 expression was increased in stricture mucosa, in the lamina propria and in CD3 positive intra-epithelial CD3 positive T-lymphocytes. Fibroblastic S100A4 staining was observed in seromuscular scar tissue. Stricture fibroblast explant culture showed significant upregulation of S100A4 expression. TGF-beta1 increased S100A4 expression in cultured ileal fibroblasts. In CCD-18 Co fibroblasts S100A4 siRNA inhibited scratch wound healing and modestly inhibited Smad3 activation. Conclusions: S100A4 expression is increased in fibroblasts as well as immune cells in CD stricture and induced by TGF-beta1. Results from knockdown experiments indicate a potential role for S100A4 in mediating intestinal fibroblast migration. (242 words).

PMID: 20489045 [PubMed - as supplied by publisher]



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