scholarly journals The Role of MicroRNAs upon Epithelial-to-Mesenchymal Transition in Inflammatory Bowel Disease

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1461 ◽  
Author(s):  
Éva Boros ◽  
István Nagy
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Acute Inflammation ◽  
Epithelial To Mesenchymal Transition ◽  
Systemic Complications ◽  
Altered Expression ◽  
Mesenchymal Transition ◽  
Multistage Carcinogenesis ◽  
Inflammatory Bowel

Increasing evidence suggest the significance of inflammation in the progression of cancer, for example the development of colorectal cancer in Inflammatory Bowel Disease (IBD) patients. Long-lasting inflammation in the gastrointestinal tract causes serious systemic complications and breaks the homeostasis of the intestine, where the altered expression of regulatory genes and miRNAs trigger malignant transformations. Several steps lead from acute inflammation to malignancies: epithelial-to-mesenchymal transition (EMT) and inhibitory microRNAs (miRNAs) are known factors during multistage carcinogenesis and IBD pathogenesis. In this review, we outline the interactions between EMT components and miRNAs that may affect cancer development during IBD.

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

2018 ◽  
Vol 13 (5) ◽  
pp. 659-668 ◽  
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.

scholarly journals Role of Altered Expression of miR-146a, miR-155, and miR-122 in Pediatric Patients with Inflammatory Bowel Disease

2016 ◽  
Vol 22 (2) ◽  
pp. 327-335 ◽  
Author(s):  
Nóra J. Béres ◽  
Dolóresz Szabó ◽  
Dorottya Kocsis ◽  
Dániel Szűcs ◽  
Zoltán Kiss ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Pediatric Patients ◽  
Altered Expression ◽  
Inflammatory Bowel

P146 OXPHOS INDUCTION IN HEALING: A CRITICAL MISSING STEP IN INFLAMMATORY BOWEL DISEASE?

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S30-S31
Author(s):  
Neeraj Kapur ◽  
Emily Bradford ◽  
Justin Thomas ◽  
Courtney Perry ◽  
Terrence Barrett
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Epithelial To Mesenchymal Transition ◽  
Healing Process ◽  
Gene Signature ◽  
Enzymatic Digestion ◽  
Mucosal Healing ◽  
Mesenchymal Transition ◽  
Atp Production ◽  
Inflammatory Bowel

Abstract Background In Inflammatory Bowel Disease (IBD), mucosal healing represents a key outcome in clinical remission. Mitochondrial dysfunction is one of the major features of IBD, which is hallmarked by increased oxidative stress and impaired ATP production. However, partial wound healing continues even with repressed mitochondrial respiration in an inflammatory environment. In this study, we demonstrate that intestinal epithelial cells (IEC) responding to colitis produce a gene signature with downregulated mitochondrial expression associated with oxidative phosphorylation (OxPHOS) and upregulate epithelial-to-mesenchymal transition (EMT). These data were consistent with the notion that EMT induced in IEC is fueled by glycolysis (repressed OxPHOS). We also wish to determine if this OxPHOS repression is present in normal healing. Methods We are actively enrolling patients with Ulcerative Colitis (UC) and normal patients into a prospective study evaluating biopsy site healing. Biopsy samples from UC patients were collected in Allprotect® or PBS. Biopsy samples collected in PBS were processed for IEC isolation using enzymatic digestion followed by flow sorting of EpCAM+ cells. To investigate the healing process in colitis and normal patients, the sigmoid colon is tattooed at initial endoscopy and 10–12 biopsies are collected in Allprotect®. Patients are brought back a week later for a flexible sigmoidoscopy. The tattooed area is examined, and biopsies are obtained from the previous biopsy sites (“biopsy of the biopsy”) and collected in Allprotect®. RNA is extracted from Allprotect® preserved tissue or isolated IECs and analyzed with RT-PCR. Results Genes corresponding to subunits of NADH dehydrogenase (Ubiquinone) of complex I (ND1, ND2, ND3, ND4, ND5 and ND6) were consistently downregulated in ulcer sites of colitis patients as compared to “biopsy of the biopsy” sites near the tattoo in normal patients. As expected, samples from colitis patients exhibited significant upregulation of inflammatory markers (iNOS, NLRP3, CCL2, RANTES, TGF-b1, CCL20 and CXCL10) compared to “biopsy of the biopsy” sites in normal patients undergoing healing. Intriguingly, epithelial marker E-cadherin was noted to be decreased in samples obtained from colitis patients with concomitant increase in mesenchymal markers (Vimentin, Snail, Twist-1 and Zeb-1) compared to previously biopsied normal controls. Discussion Our data suggests that repressed OxPHOS observed in inflamed IEC from colitis patients may serves as an inducer of EMT governing delayed but partial healing in IBD. We found this to be in stark opposition to healing in normal patients, who exhibit enhanced OxPHOS associated with rapid healing. These important findings indicate OxPHOS metabolism may be an important target for therapeutic agents to improve healing in refractory colitis.

scholarly journals Elevated Expression of AXL May Contribute to the Epithelial-to-Mesenchymal Transition in Inflammatory Bowel Disease Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Éva Boros ◽  
Zoltán Kellermayer ◽  
Péter Balogh ◽  
Gerda Strifler ◽  
Andrea Vörös ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Intestinal Inflammation ◽  
Experimental Colitis ◽  
Mesenchymal Transition ◽  
Inflammatory Bowel ◽  
Chronic Intestinal Inflammation

Understanding the molecular mechanisms inducing and regulating epithelial-to-mesenchymal transition (EMT) upon chronic intestinal inflammation is critical for understanding the exact pathomechanism of inflammatory bowel disease (IBD). The aim of this study was to determine the expression profile of TAM family receptors in an inflamed colon. For this, we used a rat model of experimental colitis and also collected samples from colons of IBD patients. Samples were taken from both inflamed and uninflamed regions of the same colon; the total RNA was isolated, and the mRNA and microRNA expressions were monitored. We have determined that AXL is highly induced in active-inflamed colon, which is accompanied with reduced expression of AXL-regulating microRNAs. In addition, the expression of genes responsible for inducing or maintaining mesenchymal phenotype, such as SNAI1, ZEB2, VIM, MMP9, and HIF1α, were all significantly induced in the active-inflamed colon of IBD patients while the epithelial marker E-cadherin (CDH1) was downregulated. We also show that, in vitro, monocytic and colonic epithelial cells increase the expression of AXL in response to LPS or TNFα stimuli, respectively. In summary, we identified several interacting genes and microRNAs with mutually exclusive expression pattern in active-inflamed colon of IBD patients. Our results shed light onto a possible AXL- and microRNA-mediated regulation influencing epithelial-to-mesenchymal transition in IBD.

The role of osteopontin (OPN/SSP1) gene variants in inflammatory bowel disease

2009 ◽  
Vol 47 (09) ◽  
Author(s):  
J Glas ◽  
J Seiderer ◽  
HP Török ◽  
B Göke ◽  
T Ochsenkühn ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Gene Variants ◽  
Inflammatory Bowel

Nutrition in inflammatory bowel disease

2009 ◽  
Vol 150 (18) ◽  
pp. 839-845 ◽  
Author(s):  
János Banai
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Fast Food ◽  
Optimal Growth ◽  
Developed Countries ◽  
Aetiological Factor ◽  
Artificial Nutrition ◽  
Food Preservatives ◽  
Inflammatory Bowel

Aetiology of inflammatory bowel disease (IBD) is complex and probably multifactorial. Nutrition has been proposed to be an important aetiological factor for development of IBD. Several components of the diet (such as sugar, fat, fibre, fruit and vegetable, protein, fast food, preservatives etc.) were examined as possible causative agents for IBD. According to some researchers infant feeding (breast feeding) may also contribute to the development of IBD. Though the importance of environmental factors is evidenced by the increasing incidence in developed countries and in migrant population in recent decades, the aetiology of IBD remained unclear. There are many theories, but as yet no dietary approaches have been proved to reduce the risk of developing IBD. The role of nutrition in the management of IBD is better understood. The prevention and correction of malnutrition, the provision of macro- and micronutrients and vitamins and the promotion of optimal growth and development of children are key points of nutritional therapy. In active disease, the effective support of energy and nutrients is a very important part of the therapy. Natural and artificial nutrition or the combination of two can be choosen for supporting therapy of IBD. The author summarises the aetiological and therapeutic role of nutrition in IBD.

scholarly journals Tu1789 – Treatment Response to Ustekinumab and Vedolizumab in Inflammatory Bowel Disease: the Predictive Role of Gut Microbiota

2019 ◽  
Vol 156 (6) ◽  
pp. S-1124
Author(s):  
Clara Caenepeel ◽  
Sara Vieira-Silva ◽  
Jorge F. Vázquez-Castellanos ◽  
Bram Verstockt ◽  
Marc Ferrante ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Gut Microbiota ◽  
Treatment Response ◽  
Bowel Disease ◽  
Predictive Role ◽  
Inflammatory Bowel

scholarly journals The Inflammatory Bowel Disease Symptom Inventory: A Patient-report Scale for Research and Clinical Application

2019 ◽  
Vol 25 (8) ◽  
pp. 1277-1290 ◽  
Author(s):  
Kathryn A Sexton ◽  
John R Walker ◽  
Laura E Targownik ◽  
Lesley A Graff ◽  
Clove Haviva ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Factor Analysis ◽  
Bowel Disease ◽  
Convergent Validity ◽  
Short Form ◽  
Self Report ◽  
Measurement Properties ◽  
Systemic Complications ◽  
Patient Reported ◽  
Inflammatory Bowel

Abstract Objectives Existing measures of inflammatory bowel disease (IBD) symptoms are not well suited to self-report, inadequate in measurement properties, insufficiently specific, or burdensome for brief or repeated administration. We aimed to develop a patient-reported outcome measure to assess a broader range of IBD symptoms. Methods The IBD Symptoms Inventory (IBDSI) was developed by adapting symptom items from existing clinician-rated or diary-format inventories; after factor analysis, 38 items were retained on 5 subscales: bowel symptoms, abdominal discomfort, fatigue, bowel complications, and systemic complications. Participants completed the IBDSI and other self-report measures during a clinic visit. A nurse administered the Harvey Bradshaw Index (HBI) for Crohn’s disease (CD) or the Powell-Tuck Index (PTI) for ulcerative colitis (UC), and a gastroenterologist completed a global assessment of disease severity (PGA). Results The 267 participants with CD (n = 142) or UC (n = 125), ages 18 to 81 (M = 43.4, SD = 14.6) were 58.1% female, with a mean disease duration of 13.9 (SD = 10.5) years. Confirmatory factor analysis supported the 5 subscales. The total scale and subscales showed good reliability and significant correlations with self-report symptom and IBD quality of life measures, the HBI, PTI, and PGA. Conclusions The IBDSI showed strong measurement properties: a supported factor structure, very good internal consistency, convergent validity, and excellent sensitivity and specificity to clinician-rated active disease. Self-report HBI and PTI items, when extracted from this measure, produced scores comparable to clinician-administered versions. The 38-item IBDSI, or 26-item short form, can be used as a brief survey of common IBD symptoms in clinic or research settings.

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