Molecular Activity of Inflammation and Epithelial-Mesenchymal Transition in the Microenvironment of Ulcerative Colitis

Gut Liver. 2024 Nov 15;18(6):1037-1047. doi: 10.5009/gnl230283. Epub 2024 Feb 22.

Abstract

Background/aims: : The genetic expression in the active inflammatory regions is increased in ulcerative colitis (UC) with endoscopic activity. The aim of this study was to investigate the molecular activity of inflammation and tissue remodeling markers in endoscopically inflamed and uninflamed regions of UC.

Methods: : Patients with UC (n=47) and controls (n=20) were prospectively enrolled at the Seoul National University Bundang Hospital. Inflamed tissue was obtained at the most active lesion, and uninflamed tissue was collected from approximately 15 cm above the upper end of the active lesion via colonoscopic biopsies. The messenger RNA expression levels of transforming growth factor β (TGF-β), interleukin (IL)-1β, IL-6, IL-17A, E-cadherin, olfactomedin-4 (OLFM4), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), vimentin, fibroblast-specific protein-1 (FSP1), and α-smooth muscle actin (SMA) were evaluated. Mucosal healing (MH) was defined according to a Mayo endoscopic score of 0, 1 or non-MH (Mayo endoscopic score of 2 or 3).

Results: : The messenger RNA expressions of TGF-β, IL-1β, OLFM4, FSP1, vimentin, and α-SMA were significantly higher, and that of E-cadherin was significantly lower in inflamed and uninflamed regions of patients with UC than those in controls. In the inflamed regions, patients in the non-MH group had significantly increased genetic expression of TGF-β, FSP1, vimentin, and α-SMA compared to patients in the MH group. Similarly, the non-MH group had significantly higher genetic expression of TGF-β, IL-1β, IL-6, vimentin, and α-SMA than the MH group in the uninflamed regions.

Conclusions: : Endoscopic activity in UC suggests inflammation and tissue remodeling of uninflamed regions similar to inflamed regions (ClinicalTrials.gov, NCT05653011).

Keywords: Colitis; Cytokines; Epithelial-mesenchymal transition; Fibrosis; ulcerative.

Publication types

  • Clinical Study

MeSH terms

  • Actins / analysis
  • Actins / genetics
  • Adult
  • Biomarkers / analysis
  • Cadherins* / genetics
  • Cadherins* / metabolism
  • Case-Control Studies
  • Cellular Microenvironment
  • Colitis, Ulcerative* / genetics
  • Colitis, Ulcerative* / pathology
  • Colon / metabolism
  • Colon / pathology
  • Colonoscopy
  • Cytokines / genetics
  • Cytokines / metabolism
  • Epithelial-Mesenchymal Transition* / genetics
  • Female
  • Humans
  • Inflammation
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Prospective Studies
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism
  • Receptors, G-Protein-Coupled / genetics
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Vimentin / analysis
  • Vimentin / metabolism

Substances

  • Actins
  • Biomarkers
  • Cadherins
  • Cytokines
  • Interleukin-1beta
  • LGR5 protein, human
  • Receptors, G-Protein-Coupled
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Vimentin

Associated data

  • ClinicalTrials.gov/NCT05653011