Faculty Opinions recommendation of Identification of epithelial to mesenchymal transition as a novel source of fibroblasts in intestinal fibrosis.

Abstract Fibrosis is a major pathway to organ injury and failure, accounting for more than one-third of deaths worldwide. Intestinal fibrosis causes irreversible and serious clinical complications, such as strictures and obstruction, secondary to a complex pathogenesis. Under the stimulation of profibrotic soluble factors, excessive activation of mesenchymal cells causes extracellular matrix deposition via canonical transforming growth factor-β/Smads signaling or other pathways (eg, epithelial-to-mesenchymal transition and endothelial-to-mesenchymal transition) in intestinal fibrogenesis. In recent studies, the importance of noncoding RNAs (ncRNAs) stands out in fibrotic diseases in that ncRNAs exhibit a remarkable variety of biological functions in modulating the aforementioned fibrogenic responses. In this review, we summarize the role of ncRNAs, including the emerging long ncRNAs and circular RNAs, in intestinal fibrogenesis. Notably, the translational potential of ncRNAs as diagnostic biomarkers and therapeutic targets in the management of intestinal fibrosis is discussed based on clinical trials from fibrotic diseases in other organs. The main points of this review include the following: • Characteristics of ncRNAs and mechanisms of intestinal fibrogenesis • Wide participation of ncRNAs (especially the emerging long ncRNAs and circular RNAs) in intestinal fibrosis, including transforming growth factor-β signaling, epithelial-to-mesenchymal transition/endothelial-to-mesenchymal transition, and extracellular matrix remodeling • Translational potential of ncRNAs in the diagnosis and treatment of intestinal fibrosis based on clinical trials from fibrotic diseases in other organs

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Resolvin D1 Prevents Epithelial-to-Mesenchymal Transition and Reduces Collagen Deposition by Stimulating Autophagy in Intestinal Fibrosis

Digestive Diseases and Sciences ◽

10.1007/s10620-021-07356-w ◽

2022 ◽

Author(s):

Cui Zeng ◽

Xinghuang Liu ◽

Danping Xiong ◽

Kaifang Zou ◽

Tao Bai

Keyword(s):

Epithelial To Mesenchymal Transition ◽

Collagen Deposition ◽

Resolvin D1 ◽

Mesenchymal Transition ◽

Intestinal Fibrosis

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Role of Epithelial-to-Mesenchymal Transition in Inflammatory Bowel Disease

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjy201 ◽

2018 ◽

Vol 13 (5) ◽

pp. 659-668 ◽

Cited By ~ 9

Author(s):

Sara Lovisa ◽

Giannicola Genovese ◽

Silvio Danese

Keyword(s):

Inflammatory Bowel Disease ◽

Wound Healing ◽

Bowel Disease ◽

Molecular Mechanisms ◽

Epithelial To Mesenchymal Transition ◽

Clinical Manifestations ◽

Mesenchymal Transition ◽

Intestinal Fibrosis ◽

Inflammatory Bowel

Abstract Intestinal fibrosis is an inevitable complication in patients with inflammatory bowel disease [IBD], occurring in its two major clinical manifestations: ulcerative colitis and Crohn’s disease. Fibrosis represents the final outcome of the host reaction to persistent inflammation, which triggers a prolonged wound healing response resulting in the excessive deposition of extracellular matrix, eventually leading to intestinal dysfunction. The process of epithelial-to-mesenchymal transition [EMT] represents an embryonic program relaunched during wound healing, fibrosis and cancer. Here we discuss the initial observations and the most recent findings highlighting the role of EMT in IBD-associated intestinal fibrosis and fistulae formation. In addition, we briefly review knowledge on the cognate process of endothelial-to-mesenchymal transition [EndMT]. Understanding EMT functionality and the molecular mechanisms underlying the activation of this mesenchymal programme will permit designing new therapeutic strategies to halt the fibrogenic response in the intestine.

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Identification of Epithelial to Mesenchymal Transition as a Novel Source of Fibroblasts in Intestinal Fibrosis

Journal of Biological Chemistry ◽

10.1074/jbc.m110.102012 ◽

2010 ◽

Vol 285 (26) ◽

pp. 20202-20212 ◽

Cited By ~ 147

Author(s):

Sarah N. Flier ◽

Harikrishna Tanjore ◽

Efi G. Kokkotou ◽

Hikaru Sugimoto ◽

Michael Zeisberg ◽

...

Keyword(s):

Epithelial To Mesenchymal Transition ◽

Mesenchymal Transition ◽

Intestinal Fibrosis

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

Mediators of Inflammation ◽

10.1155/2021/5927064 ◽

2021 ◽

Vol 2021 ◽

pp. 1-21

Author(s):

Jia Wenxiu ◽

Yang Mingyue ◽

Han Fei ◽

Luo Yuxin ◽

Wu Mengyao ◽

...

Keyword(s):

Transgenic Mice ◽

Tumor Necrosis ◽

Epithelial To Mesenchymal Transition ◽

Intestinal Inflammation ◽

Epithelial Mesenchymal Transition ◽

Lymphoid Cells ◽

Inflammatory Factors ◽

Mesenchymal Transition ◽

Intestinal Fibrosis

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.

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