In Crohn{'}s disease fibrosis reduced expression of the miR-29 family enhances collagen expression in intestinal fibroblasts

Intestinal fibrosis with stricture formation is a complication of Crohn’s disease (CD) that may mandate surgical resection. Accurate biomarkers that reflect the relative contribution of fibrosis to an individual stricture are an unmet need in managing patients with CD. The microRNA (miR)-29 family has been implicated in cardiac, hepatic and pulmonary fibrosis. We investigated the expression of miR-29a, miR-29b and miR-29c in mucosa overlying a stricture in CD patients (SCD) paired with mucosa from non-strictured areas (NSCD). There was significant down-regulation of the miR-29 family in mucosa overlying SCD compared to mucosa overlying NSCD. MiR-29b showed the largest fold-decrease and was selected for functional analysis. Over-expression of miR-29b in CD fibroblasts led to a down-regulation of collagen I and III transcripts and collagen III protein, but did not alter matrix metalloproteinase (MMP)-3, MMP-12 and tissue inhibitor of metalloproteinase (TIMP)-1 production. TGF-β1 up-regulated collagen I and III transcripts and collagen III protein as a consequence of the down-regulation of miR-29b and TGF-β1-induced collagen expression was reversed by exogenous overexpression of miR-29b. Furthermore, serum levels of miR-29 were lower in patients with stricturing disease compared to those without. These data implicate the miR-29 family in the pathogenesis of intestinal fibrosis in CD and provides impetus for the further evaluation of the miR-29 family as biom...
Source: Clinical Science - Category: Biomedical Science Authors: Source Type: research