OC.07.1 MICRO-RNA EXPRESSION PROFILING IDENTIFIES MIR-29B AS A RELEVANT PRO-FIBROGENIC FACTOR IN CROHN'S DISEASE INTESTINAL STRICTURES

differentiation of human colonic fibroblasts and epithelial cells into myofibroblasts. Methods: Chronic colonic fibrosis was induced in C57BL/6 mice by successive 2.5% (w/v) DSS administration in drinking water for 6 weeks. After 6 weeks, the therapeutic effect of GED (30mg/kg/d), daily administered by oral gavage, was assessed macroscopically (weight/length of the colon, edema, ulcers, adhesions, thickness, dilatation), histologically (inflammatory infiltrate, collagen deposition) and biologically (colonic alpha-SMA, collagen I, TGFbeta1, CTGF, Smad3 and IL-13, by immunohistochemistry and immunoblotting). Differentiation of fibroblasts and intestinal epithelial cells (IECs) into myofibroblasts was induced by 4 day of TGFbeta administration (1 ng/mL and 10 ng/mL, respectively). Expression of aplha-SMA, fibronectine and the specific IECs markers (A33 and cytokeratin) was evaluated by quantitative RT-PCR. In vitro collagen deposition was observed by Picrosirius red staining. Results: In DSS-treated mice GED induced a significant 26% decrease of the colon weight/length ratio (p < 0.05) and ameliorated macroscopic and microscopic lesions determining 35% reduction of total macroscopic score (p < 0.05) and 91% (p < 0.01) of histological score. GED regulated the increased DSS-induced tissue expression of specific fibrotic markers, mainly Collagen I-III (48% p < 0.05), CTGF (35%, p < 0.05) and IL-13 (50%, p < 0.01). GED reduced mRNA expression of differentiation markers of fibroblasts and IECs, alpha-SMA (18%, p < 0.05 and 16%, p < 0.05, respectively) and fibronectine (45%, p < 0.005 and 67%, p < 0.005, respectively) and restored specific IECs markers. GED determined a 65% reduction of TGFbetainduced collagen deposition (p < 0.05), both in fibroblast and IECs. Conclusions: GED ameliorates the intestinal fibrosis in a DSS-induced chronic colitis in mice by controlling the main molecular and cellular mechanisms involved.