COMP-angiopoietin-1 ameliorates inflammation-induced lymphangiogenesis in dextran sulfate sodium (DSS)-induced colitis model

Alterations in the intestinal lymphatic network are pathological processes as related to inflammatory bowel disease (ibd). in this study, we demonstrated that reduction in inflammation-induced lymphangiogenesis ameliorates experimental acute colitis. a soluble and stable angiopoietin-1 (ang1) variant, comp-ang1, possesses anti-inflammatory and angiogenic effects. we investigated the effects of comp-ang1 on an experimental colonic inflammation model. experimental colitis was induced in mice by administering 3% dextran sulfate sodium (dss) via drinking water. we determined body weight, disease activity indices, histopathological scores, lymphatic density, anti-er-hr3 staining, and the expression of members of the vascular endothelial growth factor (vegf) family and various inflammatory cytokines in the mice. the density of lymphatic vessel endothelial hyaluronan receptor 1 (lyve-1) and vegfr-3-positive lymphatic vessels increased in mice with dss-induced colitis. we observed that comp-ang1-treated mice showed less weight loss, fewer clinical signs of colitis, and longer colons than ade-dss-treated mice. comp-ang1 also significantly reduced the density of lyve-1-positive lymphatic vessels and the disruption of colonic architecture that is normally associated with colitis and repressed the immunoregulatory response. further, comp-ang1 treatment reduced both m1 and m2 macrophage infiltration into the inflamed colon, which involved inhibition of vegf-c and d expression. thus, comp-ang1, which acts by reducing inflammation-induced lymphangiogenesis, be used as a novel therapeutic for the treatment of ibd and other inflammatory diseases.