Tu1827 Low Mitochondrial Activity Within Intestinal Inflammation Increases Lipid Droplets (LDs) via Loss of FOXO3 to Facilitate Inflammatory Mediators

Abstract

son's trichrome blue, and for myofibroblast proliferation by immunostaining for aSMA; and 3) Cre-mouse lines expressing green fluorescent proteins (GFP) to label intestinal epithelial cells (Tomatof:Villin-cre mice) and epithelial stem cells (Tomatof:Lgr5-cre mice) for fibroblasts and myofibroblasts using the loxp/Cre system. Results: 1) Increased numbers of myofibroblasts were present in the submucosa of the small intestine from Crohn's patients, suggesting that fibrogenesis initiates at an early stage of Crohn's disease; 2) collagen deposition occurred in the submucosal layer of mouse colon as early as 2 weeks after TNBS treatment. Prolonged treatment with TNBS progressively increased collagen deposition in all intestinal layers, leading to severe intestinal fibrosis and stricture. We also found that myofibroblast proliferation detected by aSMA staining was increased in these layers, particularly in the submucosal layer which was markedly prevented by rapamyicn; and 3) an increase in GFPlabeled Lgr5+cells migrated to the lamina propria, submucosa of the mouse colon, whereas intestinal epithelial cells from Tomatof:Villin-cre mice remained within the epithelial layer. Conclusions: fibrogenesis occurs early or at least concomitant to chronic inflammation. A new route of fibrogenesis may directly promote differentiation of Lgr5+ cells to fibrogenic cells in TNBS induced intestinal fibrosis.