An increasing number of studies indicate that epithelial to mesenchymal transition (EMT) is involved in intestinal fibrosis. Exploration into the origins of myofibroblasts may provide an opportunity to develop effective treatments in intestinal fibrosis.
Myofibroblasts are important effector cells for the deposition of ECM in intestinal fibrosis, and their sources are varied. Identifying effective treatment for intestinal fibrosis-induced by IBD has become the focus of investigations worldwide. Ulcerative colitis (UC) has long been believed to be a nonfibrotic disease however, recent studies have found a certain degree of submucosal fibrosis in almost all colon resection specimens from patients with UC. Unfortunately, the recurrence rate is as high as 70%. As many as one-third of patients with Crohn’s disease (CD) develop end-stage fibrotic disease characterized by stenosis and organ failure, and 80% of cases require surgical resection of the fibrotic intestinal tissue. In patients with inflammatory bowel disease (IBD), recurrent intestinal inflammation triggers mucosal healing reactions, leading to extracellular matrix (ECM) deposition in the intestine to form intestinal fibrosis. This new knowledge enables us to better understand the pathogenesis of intestinal fibrosis and identify new therapeutic targets for its treatment. TL1A participates in the formation and process of EMT in intestinal fibrosis. Furthermore, TL1A-induced EMT can be influenced by anti-TL1A antibody or BMP-7 in vitro. 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. Transgenic mice with high expression of TL1A were more sensitive to dextran sodium sulfate and exhibited severe intestinal inflammation and fibrosis.
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). In addition, transgenic mice expressing high levels of TL1A in lymphoid cells were used to further investigate the mechanism of TL1A in intestinal fibrosis.
Furthermore, the human colorectal adenocarcinoma cell line, HT-29, was stimulated with TL1A, anti-TL1A antibody, or BMP-7 to assess EMT process. The expression levels of TL1A and EMT-related markers in intestinal tissues were evaluated. Colonic specimens were obtained from patients with inflammatory bowel disease (IBD) and control individuals. The purpose of this study was to elucidate the possible contribution of TL1A in onset and progression of intestinal inflammation and fibrosis through EMT. 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. Recent evidences reveal that epithelial to mesenchymal transition (EMT) exacerbates the process of intestinal fibrosis.
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