Endothelin and vascular remodelling in colitis pathogenesis—Appendicitis and appendectomy limit colitis by suppressing endothelin pathways

Purpose Appendicitis and appendectomy(AA), when done at a young age, offer protection against inflammatory bowel disease (IBD) development in later life. However, IBD pathogenesis involves both immunological and vascular abnormalities. Using the first murine model of AA (developed by us), we aimed to determine the role of AA in modulating vascular remodelling mediated by endothelin activity in IBD. Methods Mice with two laparotomies each served as controls (sham-sham or SS). Distal colons were harvested (four AA group colons, four SS group colons), and RNA extracted from each. The RNA was subjected to microarray analysis and RT-PCR validation. Gene set enrichment analysis (GSEA) software was used to further analyze the microarray data. Results Gene expression of seven genes closely associated with endothelin activity was examined in distal colons 3 days post-AA and 28 days post-AA. While there were no gene expression changes 3 days post-AA, the genes EDN1 (0.7-fold), EDN2 (0.8-fold) and ECE2 (0.8-fold) were downregulated (* p value