Intestinal Permeability and Approach to Healing the Gut

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Gastroenterology & Hepatology".

Deadline for manuscript submissions: closed (30 March 2023) | Viewed by 2813

Special Issue Editor


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Guest Editor
Department of Pathology and Molecular Medicine/FARNCOMBE Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada
Interests: Crohn’s disease; ulcerative colitis; colitis-associated colorectal cancer; barrier dysfunction

Special Issue Information

Dear Colleagues,

Gut health is of prime importance to maintaining a healthy daily routine, as an upset gut affects our overall functioning because of its connections with the brain. Despite the mass of studies on gastrointestinal (GI) disorders such as colitis, celiac disease and irritable bowel syndrome (IBS), the exact etiology of many disorders remains unknown. One of the factors known to be associated with various GI disorders is intestinal permeability. Alterations in tight junction (TJ) and adherent junction (AJ) proteins have been shown to destabilize cell contacts and facilitate the invasion of pathogens, leading to chronic inflammatory conditions. Furthermore, inflammatory cytokines destabilize junction molecules by internalization or proteolysis via activating the mediators of signaling pathways such as small GTPase. Apart from other various non-invasive strategies, one of the approaches to healing gastrointestinal conditions resulting from changes in gut permeability is by restoring the altered junction molecules.

The journal Medicina, under the section “Gastrointestinal Disorders”, is inviting gastroenterologists and basic science researchers who have been involved in studying various gastrointestinal disorders to share their novel findings on the status of junction proteins toward advancing our knowledge in understanding the pathogenesis of the various disorders. Furthermore, submission on the role of immune dysregulation, microbiota changes and signaling pathways identified in the initiation and perpetuation of the disorders will be appreciated.

Dr. Suhrid Banskota
Guest Editor

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Keywords

  • inflammatory bowel disease
  • irritable bowel syndrome
  • celiac disease
  • gut–brain axis
  • altered gut microbiota
  • inflammatory cytokines
  • immune dysregulation
  • altered GI secretions
  • epigenetic changes in junction proteins
  • barrier function in gut

Published Papers (1 paper)

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Research

17 pages, 3547 KiB  
Article
Protective Effect of Irsogladine against Aspirin-Induced Mucosal Injury in Human Induced Pluripotent Stem Cell-Derived Small Intestine
by Takuya Kanno, Takahito Katano, Isamu Ogawa, Takahiro Iwao, Tamihide Matsunaga and Hiromi Kataoka
Medicina 2023, 59(1), 92; https://doi.org/10.3390/medicina59010092 - 31 Dec 2022
Cited by 1 | Viewed by 2281
Abstract
Background and Objectives: Acetylsalicylic acid (ASA) is widely used for preventing cerebrovascular and cardiovascular diseases. Gastrointestinal (GI) tract injury is one of the major complications of aspirin use, potentially leading to severe GI bleeding. However, no drugs for preventing aspirin-induced small intestinal [...] Read more.
Background and Objectives: Acetylsalicylic acid (ASA) is widely used for preventing cerebrovascular and cardiovascular diseases. Gastrointestinal (GI) tract injury is one of the major complications of aspirin use, potentially leading to severe GI bleeding. However, no drugs for preventing aspirin-induced small intestinal injury have been developed. The aim of this study was to establish a human experimental model for investigating aspirin-induced small intestinal mucosal injury. In addition, we evaluated the protective effect of Irsogladine against aspirin-induced small intestinal mucosal injury using human induced pluripotent stem cell-derived 2D monolayer crypt-villus structural small intestine (2D-hiPSC-SI). Materials and Methods: Human iPS cell-derived intestinal organoids were seeded and cultured in Air-liquid interface. The permeability of 2D-hiPSC-SI was evaluated using Lucifer yellow. Changes in structure and mucosal permeability of 2D-hiPSC-SI after addition of aspirin were confirmed over time, and changes in intestinal epithelium-related markers were evaluated by real-time qPCR and Immunofluorescence staining. The effect of Irsogladine on prevention of aspirin mucosal injury was examined by adding Irsogladine to the culture medium. Results: Cultured 2D-hiPSC-SI showed multi-lineage differentiation into small intestinal epithelium comprised of absorptive cells, goblet cells, enteroendocrine cells, and Paneth cells, which express CD10, MUC2, chromogranin A, and lysozyme, respectively. RNA in situ hybridization revealed intestinal stem cells that express Lgr5. ASA administration induced an increase in the mucosal permeability of 2D-hiPSC-SI. ASA-injured 2D-hiPSC-SI showed decreased mRNA expression of multi-lineage small intestinal cell markers as well as intestinal stem cell marker Lgr5. Administration of Irsogladine on the basal side of the 2D-hiPSC-SI resulted in significant increases in Mki67 and Muc2 mRNA expression by 2D-hiPSCs at 48 h compared with the control group. Administration of 400 µg/mL Irsogladine to the ASA-induced small intestinal injury model resulting in significantly decreased mucosal permeability of 2D-hiPSC-SI. In immunofluorescence staining, Irsogladine significantly increased the fluorescence intensity of MUC2 under normal conditions and administration of 400 µg/mL ASA. Conclusions: we established a novel ASA-induced small intestinal injury model using human iPSC-derived small intestine. Irsogladine maintains mucosal permeability and goblet cell differentiation against ASA-induced small intestinal injury. Full article
(This article belongs to the Special Issue Intestinal Permeability and Approach to Healing the Gut)
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