Fibrotic and Vascular Remodelling of Colonic Wall in Patients with Active Ulcerative Colitis

Background and Aims: Intestinal fibrosis is a complication of inflammatory bowel disease (IBD). Although fibrostenosis is a rare event in ulcerative colitis (UC), there is evidence that a fibrotic rearrangement of colon occurs in the later stages. This is a retrospective study aimed at examining the histopathological features of colonic wall in both short-lasting (SL) and long-lasting (LL) UC. Methods: Surgical samples of left colon from non-stenotic SL (≤ 3 years, n=9) and LL (≥ 10 years, n=10) UC patients with active disease were compared to control colonic tissues from cancer patients without UC (n=12) to assess: collagen and elastic fibers by histochemistry; vascular networks (CD31/CD105/nestin) by immunofluorescence; parameters of fibrosis [type I and III collagen, fibronectin, RhoA, alpha-smooth muscle actin (α-SMA), desmin, vimentin] and proliferation [proliferating nuclear antigen (PCNA)] by Western blot and/or immunolabelling. Results: Colonic tissue from both SL-UC and LL-UC showed tunica muscularis thickening and transmural activated neovessels (displaying both proliferating CD105-positive endothelial cells and activated nestin-positive pericytes), as compared to controls. In LL-UC the increased collagen deposition was associated with an up-regulation of tissue fibrotic markers (collagen I and III, fibronectin, vimentin, RhoA), an enhancement of proliferation (PCNA) and, along with a loss of elastic fibers, a rearrangement of the tunica muscularis towards a fibrotic phenotype. Conclusions: A significant transmural fibrotic thickening occurs in colonic tissue from LL-UC, together with a cellular fibrotic switch in the tunica muscularis. A full-thickness angiogenesis is also evident in both SL- and LL-UC with active disease, as compared to controls.