OP027 SUCNR1 receptor mediates intestinal fibrosis
J. Cosin-Roger1,2*, D. Ortiz-Masia2, D.C. Macias-Ceja1, L. Gisbert-Ferrandiz2, P. Salvador2, M. Hausmann3, G. Rogler3, S. Calatayud2, M.D. Barrachina2
1Fisabio, Hospital Dr Peset, Valencia, Spain, 2University of Valencia, Valencia, Spain, 3University of Zurich, Gastroenterology, Zurich, Switzerland
Intestinal fibrosis is a common complication associated with Crohn’s Disease (CD) which cannot be reverted with any drug and forces repeated surgery. It has been reported that succinate, a metabolite accumulated in inflammatory pathologies, plays an important role in the activation of synovial fibroblasts and hepatic stellate cells through its receptor called SUCNR1 or GPR91. We aim to analyse the relevance of SUCNR1 receptor in intestinal fibrosis.
Intestinal resections from CD patients and colon carcinoma patients were obtained and the expression of SUCNR1 and α-sma were analysed by immunostaining. Primary intestinal fibroblasts from human resections or from colon of wild-type (WT) or SUCNR1−/− (KO) mice were isolated, maintained in culture and treated with different concentrations (0, 0.1, 0.5, 1, and 5 mM) of succinate for 24 h. Intestinal fibrosis was induced in vivo introducing one intestinal graft from WT or KO mice into the neck of a receptor mice for 7 days. The expression of pro-fibrotic markers was analysed by qPCR. Sirius Red staining was performed and the collagen layer was quantified using ImageJ. Results are expressed by mean ± SEM (
SUCNR1 is expressed in epithelial cells and α-sma+ cells of intestinal resections from CD patients. The SUCNR1 expression positively and significantly correlates with the expression of α-sma (
An increased expression of SUCNR1 receptor is detected in fibroblasts from CD patients the activation of which induces a pro-fibrotic effect. This receptor mediates murine intestinal fibrosis and we propose its blockade as a new pharmacological target in CD treatment.