Effect and Mechanism of TL1A Expression on Epithelial-Mesenchymal Transition during Chronic Colitis-Related...

Area of Science:

• Gastroenterology and Immunology
• Molecular Biology and Pathology

Background:

• Epithelial to mesenchymal transition (EMT) is increasingly recognized as a key driver of intestinal fibrosis.
• Tumor necrosis factor-like ligand 1A (TL1A), a member of the TNF superfamily, is implicated in colonic inflammation and fibrosis.
• The specific role of TL1A in mediating intestinal fibrosis through EMT remains to be fully elucidated.

Purpose of the Study:

• To investigate the contribution of TL1A to the onset and progression of intestinal inflammation and fibrosis.
• To determine if TL1A-induced intestinal fibrosis is mediated through the process of EMT.

Main Methods:

• Analysis of colonic specimens from inflammatory bowel disease (IBD) patients and controls to assess TL1A and EMT marker expression.
• In vitro studies using HT-29 cells stimulated with TL1A, anti-TL1A antibody, or BMP-7 to evaluate EMT.
• In vivo studies using transgenic mice overexpressing TL1A to examine mechanisms of intestinal fibrosis.

Main Results:

• Elevated TL1A expression in IBD patients correlated with decreased epithelial marker (E-cadherin) and increased interstitial markers (FSP1, α-SMA), indicating EMT.
• TL1A-overexpressing mice showed heightened sensitivity to DSS, leading to severe intestinal inflammation and fibrosis, involving the TGF-β1/Smad3 pathway.
• TL1A-induced EMT was modulated by anti-TL1A antibody and BMP-7 in vitro, with increased IL-13 and EMT transcriptional factors (ZEB1, Snail1) observed in transgenic mice.

Conclusions:

• TL1A plays a significant role in the development and progression of EMT in intestinal fibrosis.
• These findings enhance our understanding of intestinal fibrosis pathogenesis.
• TL1A emerges as a potential therapeutic target for treating intestinal fibrosis.