Non-coding transcribed ultraconserved region uc.290 in colon mucosa promotes intestinal fibrosis in chronic active ulcerative colitis

Dig Liver Dis. 2024 May 11:S1590-8658(24)00737-0. doi: 10.1016/j.dld.2024.04.036. Online ahead of print.

Abstract

Background and aims: TGF-β1 induces epithelial-mesenchymal transition (EMT) and leads to intestinal fibrosis in ulcerative colitis (UC). We aimed to investigate the expression of transcribed ultraconserved region uc.290 in chronic UC and its role in intestinal fibrosis.

Methods: Colon specimens were taken from thirty chronic active UC, chronic inactive UC and healthy controls respectively. Modified Mayo score, expressions of uc.290, TGF-β1, EMT biomarkers (Vimentin, α-SMA and E-cadherin) and intestinal fibrosis biomarker (collagen Ⅲ) in colon biopsy specimens were determined in human. Expressions of TGF-β1, EMT biomarkers and collagen Ⅲ were determined in uc.290 overexpressed or silenced epithelial colon cells (HT29).

Results: Uc.290, TGF-β1 and collagen Ⅲ were overexpressed, and EMT was prominent in chronic active UC. Uc.290 level had a positive correlation with modified Mayo score in chronic active UC. TGF-β1 and collagen Ⅲ were overexpressed, and EMT was prominent in uc.290 overexpressed HT29 cells.

Conclusions: Uc.290 was overexpressed in chronic active UC and might promote intestinal fibrosis by TGF-β1/EMT/collagen Ⅲ pathway.

Keywords: Epithelial-mesenchymal transition; Intestinal fibrosis; Transcribed ultraconserved region; Ulcerative colitis.