Background and Aims. Recent evidences reveal that epithelial to mesenchymal transition (EMT) exacerbates the process of intestinal fibrosis. Tumor necrosis factor-like ligand 1A (TL1A) is a member of the tumor necrosis family (TNF), which can take part in the development of colonic inflammation and fibrosis by regulating immune response or inflammatory factors. The purpose of this study was to elucidate the possible contribution of TL1A in onset and progression of intestinal inflammation and fibrosis through EMT. Methods. Colonic specimens were obtained from patients with inflammatory bowel disease (IBD) and control individuals. The expression levels of TL1A and EMT-related markers in intestinal tissues were evaluated. Furthermore, the human colorectal adenocarcinoma cell line, HT-29, was stimulated with TL1A, anti-TL1A antibody, or BMP-7 to assess EMT process. In addition, transgenic mice expressing high levels of TL1A in lymphoid cells were used to further investigate the mechanism of TL1A in intestinal fibrosis. Results. High levels of TL1A expression were detected in the intestinal specimens of patients with ulcerative colitis and Crohn’s disease and were negatively associated with the expression of an epithelial marker (E-cadherin), while it was positively associated with the expression of interstitial markers (FSP1 and α-SMA). Transgenic mice with high expression of TL1A were more sensitive to dextran sodium sulfate and exhibited severe intestinal inflammation and fibrosis. Additionally, the TGF-β1/Smad3 pathway may be involved in TL1A-induced EMT, and the expression of IL-13 and EMT-related transcriptional molecules (e.g., ZEB1 and Snail1) was increased in the intestinal specimens of the transgenic mice. Furthermore, TL1A-induced EMT can be influenced by anti-TL1A antibody or BMP-7 in vitro. Conclusions. TL1A participates in the formation and process of EMT in intestinal fibrosis. This new knowledge enables us to better understand the pathogenesis of intestinal fibrosis and identify new therapeutic targets for its treatment.

中文翻译：

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TL1A表达对慢性结肠炎相关肠纤维化上皮-间质转化的影响及机制

背景和目标。最近的证据表明，上皮间质转化（EMT）加剧了肠纤维化的过程。肿瘤坏死因子样配体1A（TL1A）是肿瘤坏死家族（TNF）的成员，可通过调节免疫反应或炎症因子参与结肠炎症和纤维化的发展。本研究的目的是阐明 TL1A 通过 EMT 在肠道炎症和纤维化的发生和进展中的可能贡献。方法. 结肠标本取自炎症性肠病 (IBD) 患者和对照个体。评估肠组织中 TL1A 和 EMT 相关标志物的表达水平。此外，用 TL1A、抗 TL1A 抗体或 BMP-7 刺激人结肠直肠癌细胞系 HT-29 以评估 EMT 过程。此外，利用在淋巴细胞中表达高水平 TL1A 的转基因小鼠进一步研究 TL1A 在肠纤维化中的作用机制。结果。在溃疡性结肠炎和克罗恩病患者的肠道标本中检测到高水平的 TL1A 表达，并且与上皮标志物（E-钙粘蛋白）的表达呈负相关，而与间质标志物（FSP1 和α- SMA）。TL1A高表达的转基因小鼠对葡聚糖硫酸钠更敏感，并表现出严重的肠道炎症和纤维化。此外，TGF- β1 /Smad3通路可能参与TL1A诱导的EMT，转基因小鼠肠道标本中IL-13和EMT相关转录分子（如ZEB1和Snail1）的表达增加。此外，TL1A 诱导的 EMT 可以在体外受到抗 TL1A 抗体或 BMP-7的影响。结论。TL1A参与肠纤维化中EMT的形成和过程。这一新知识使我们能够更好地了解肠纤维化的发病机制并确定其治疗的新治疗靶点。