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

J Crohns Colitis. 2016 Oct;10(10):1194-204. doi: 10.1093/ecco-jcc/jjw076. Epub 2016 Mar 19.

Abstract

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 the colon occurs in the later stages. This is a retrospective study aimed at examining the histopathological features of the 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 with control colonic tissues from cancer patients without UC [n = 12] to assess: collagen and elastic fibres by histochemistry; vascular networks [CD31/CD105/nestin] by immunofluorescence; parameters of fibrosis [types 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 with 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 fibres, 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 with controls.

Keywords: Active disease; colonic muscle remodelling; intestinal angiogenesis; intestinal fibrosis; ulcerative colitis.

MeSH terms

  • Acute Disease
  • Adult
  • Aged
  • Biomarkers / metabolism
  • Blotting, Western
  • Case-Control Studies
  • Colitis, Ulcerative / pathology*
  • Colon / blood supply
  • Colon / metabolism
  • Colon / pathology*
  • Disease Progression
  • Female
  • Fibrosis
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Single-Blind Method
  • Vascular Remodeling*

Substances

  • Biomarkers