RAGE: A NEW FRONTIER IN INTESTINAL FIBROSIS

S. Speca, M. Body-Malapel, C. Fradin, M. Djouina, E. Boulanger, AM. Schmidt, P. Desreumaux and C. Vignal Background: Our aim was to determine the role of RAGE in intestinal fibrogenesis. Methods: Fibrosis was induced in WT and RAGE-/- mice by administration of dextran sulfate sodium. The colon was scored for macroscopic lesions and subject to Hematoxylin/Eosin staining, to assess the degree of inflammation, and Picrosirius red for collagen deposition. mRNA expression of the profibrotic mediator, Tgf-β1, and ECM components, collagen types I-III (Col1A1 gene) and fibronectin (FN-1 gene), were evaluated by RT-qPCR. Results: Compared to WT mice, DSS-treated RAGE-/- mice showed a significant decrease in colon weight/length ratio, and macroscopic and microscopic scores. Tgf-β1, Col1A1 and FN-1 mRNA expressions were significantly increased by the DSS administration in WT mice colon, whereas it was unchanged in RAGE-/- mice. Conclusion: This study represents a first insight into the involvement of RAGE in intestinal fibrosis in mice. The potential profibrotic role of RAGE could shed light into the complex and dynamic fibrogenic processes and pave the way for new anti-fibrotic agents.