Downregulation of trefoil factor‑3 expression in the rectum is associated with the development of ulcerative colitis‑associated cancer

Kondo, Satoru; Araki, Toshimitsu; Toiyama, Yuji; Kawamura, Mikio; Okugawa, Yoshinaga; Okita, Yoshiki; Saigusa, Susumu; Inoue, Yasuhiro; Uchida, Keiichi; Mohri, Yasuhiko; Kusunoki, Masato

doi:10.3892/ol.2018.9120

Cited by 9 publications

(6 citation statements)

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“…TFF3 enhances the integrity of the mucosal epithelial surface and promotes the process of reconstitution through cell migration (7). The interaction between TFF3 and mucins has also been reported to protect intestinal epithelia from injuries, maintaining mucosal barrier function (26). Furthermore, mitogenic effects of TFF3 have been identified in vitro in primary cell culture, and TFF3 has been demonstrated to inhibit apoptosis, induce cellular invasion, act as an inflammatory modulator and exhibit pro-angiogenic activity (27)(28)(29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

Extracellular production of recombinant sus scrofa trefoil factor 3 by Brevibacillus choshinensis

Wen

et al. 2020

Exp Ther Med

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Trefoil factor 3 (TFF3) is involved in cell adhesion, motility and apoptosis, regulates mucosal immunity and maintains the functional integrity of intestinal epithelia. The upregulation of TFF3 expression in the weaning rat intestine attracted our interest. The present study hypothesized that TFF3 may serve a role in preventing diarrhea in weaning piglets, which is an important consideration in the pig farming industry. Previous recombinant TFF3 protein expression yields obtained from Escherichia coli were too low and the bioactivity of the protein was poor. Hence, this expression system was unsuitable for industrial applications. The present study explored the production of recombinant sus scrofa TFF3 in a Brevibacillus choshinensis (B. choshinensis) expression system, aiming to enhance the expression level of bioactive protein. To achieve this, the sus scrofa TFF3-encoding gene fragment was fused into an E. coli-Brevibacillus shuttle vector pNCMO2. High levels of TFF3 (30 mg/l) were produced and secreted into the B. choshinensis culture medium in soluble form with a molecular mass of 13.6 kDa and high immunoreactivity in western blotting. Thus, Brevibacillus may be used to produce useful mucosal factors for biochemical analyses and mucosal protection, and in industrial applications to produce novel inhibitors of diarrhea.

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Section: Discussionmentioning

confidence: 99%

Extracellular production of recombinant sus scrofa trefoil factor 3 by Brevibacillus choshinensis

Wen

et al. 2020

Exp Ther Med

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“…Експресія TFF3, на відміну від експресії MUC2 і MUC4, у всіх групах була вираженою. Визначений дисбаланс експресії наведених пептидів на сьогодні залишається нез'ясова ним, але існує точка зору, що висока експресія трефоїлового фактора може розглядатися як компенсаторний механізм протективної бар'єр ної функції СО оболонки при запаленні [1,9,10,13,21].…”

Section: результати дослідження та їх обговоренняunclassified

Colon epithelial barrier state in children with varios types of ulcerative colitis clinical forms

Денисова¹,

Zadorojna²,

Bukulova³

et al. 2021

UJPP

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Purpose — analyse the state of the epithelial barrier of the colon in children with different clinical forms. Materials and methods. 42 children with acute chronic colitis were examined, including 28 with ulcerative colitis (14 with active total form, 14 with moderately active segmental); and 14 with chronic non-specific opaque colitis formed a comparison group. Laboratory methods were performed on all patients — hemogram, protein-gram, blood biochemistry, fecal calprotectin concentration; endoscopic examination with biopsy of all colon regions and histological examination of biopts. Results. The clinical manifestations of ulcerative colitis (UC) during the acute period were assessed by the Paediatric Activity Index (PUCAI) and depended on the localization and activity of the inflammatory process. The average for active colitis was found to be 50.2±1.8, moderate to 35.3±1.7, minimum to 24.1±1.2, but for children with total active inflammation 19 per cent of patients had the highest rates: 65, which corresponded to clinical signs of ulcerative colitis, accompanied by unidirectional changes of surface (dystrophic changes of epithelium, crypt deformation, reduced number of flax cells) and deep (diffuse inflammatory infiltration of its own plate, presence of crypt abscesses, cryptites, vascular dilation) structures of the mucous membrane of the large intestine, which are more pronounced in the active total forms of ulcerative colitis. The period of UC exacerbation is characterized by the violation of the epithelial barrier mucous membrane colon due to reduced mucus synthesis and changes in its biochemical properties, low secretory (MUC2) and membrane-associated (MUC4) expression Mucins, mainly in the active total forms of UC, loss of the regulatory effect of the club peptide on regeneration and protection of the mucous membrane of the intestine. Conclusions. Studies based on a pathogenetic approach to determining the cause of the exacerbation of the disease have shown evidence of a significant role in the epithelial barrier of the colon membrane, This is a significant addition to the known knowledge of ulcerative colitis pathogenesis in childhood. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of these Institutes. The informed consent of the patient was obtained for conducting the studies. The authors declare no conflicts of interests. Key words: ulcerative colitis, children, epithelial barrier, mucins, clubs.

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“…Trefoil factors (TFFs), which are secreted from goblet cells, are known to be the initiators of mucosal healing by promoting restitution and by suppressing IEC apoptosis[53]. Down regulated TFFs in goblet cells have been implicated in the pathogenesis of IBD[54-56] (Figure 1A).…”

Section: Epithelial Barrier Dysfunctions: a Pressing Need For Intestimentioning

confidence: 99%

Intestinal enteroids/organoids: A novel platform for drug discovery in inflammatory bowel diseases

Yoo¹,

Donowitz²

2019

WJG

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The introduction of biologics such as anti-tumor necrosis factor (TNF) monoclonal antibodies followed by anti-integrins has dramatically changed the therapeutic paradigm of inflammatory bowel diseases (IBD). Furthermore, a newly developed anti-p40 subunit of interleukin (IL)-12 and IL-23 (ustekinumab) has been recently approved in the United States for patients with moderate to severe Crohn’s disease who have failed treatment with anti-TNFs. However, these immunosuppressive therapeutics which focus on anti-inflammatory mechanisms or immune cells still fail to achieve long-term remission in a significant percentage of patients. This strongly underlines the need to identify novel treatment targets beyond immune suppression to treat IBD. Recent studies have revealed the critical role of intestinal epithelial cells (IECs) in the pathogenesis of IBD. Physical, biochemical and immunologic driven barrier dysfunctions of epithelial cells contribute to the development of IBD. In addition, the recent establishment of adult stem cell-derived intestinal enteroid/organoid culture technology has allowed an exciting opportunity to study human IECs comprising all normal epithelial cells. This long-term epithelial culture model can be generated from endoscopic biopsies or surgical resections and recapitulates the tissue of origin, representing a promising platform for novel drug discovery in IBD. This review describes the advantages of intestinal enteroids/organoids as a research tool for intestinal diseases, introduces studies with these models in IBD, and gives a description of the current status of therapeutic approaches in IBD. Finally, we provide an overview of the current endeavors to identify a novel drug target for IBD therapy based on studies with human enteroids/organoids and describe the challenges in using enteroids/organoids as an IBD model.

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Downregulation of trefoil factor‑3 expression in the rectum is associated with the development of ulcerative colitis‑associated cancer

Cited by 9 publications

References 50 publications

Extracellular production of recombinant sus scrofa trefoil factor 3 by Brevibacillus choshinensis

Extracellular production of recombinant sus scrofa trefoil factor 3 by Brevibacillus choshinensis

Colon epithelial barrier state in children with varios types of ulcerative colitis clinical forms

Intestinal enteroids/organoids: A novel platform for drug discovery in inflammatory bowel diseases

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