Oncel S, Basson MD. Gut homeostasis, injury, and healing: New therapeutic targets. World J Gastroenterol 2022; 28(17): 1725-1750 [PMID: 35633906 DOI: 10.3748/wjg.v28.i17.1725]
Corresponding Author of This Article
Marc D Basson, MD, PhD, Professor, Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, 1301 North Columbia Road, Grand Forks, ND 58202, United States. marc.basson@und.edu
Research Domain of This Article
Research & Experimental Medicine
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. May 7, 2022; 28(17): 1725-1750 Published online May 7, 2022. doi: 10.3748/wjg.v28.i17.1725
Gut homeostasis, injury, and healing: New therapeutic targets
Sema Oncel, Marc D Basson
Sema Oncel, Marc D Basson, Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
Marc D Basson, Department of Surgery, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
Marc D Basson, Department of Pathology, University of North Dakota School of Medicine and Health Sciences, Grand Forks, ND 58202, United States
Author contributions: Oncel S and Basson MD equally contributed to this manuscript with regards to the conception and structure of the manuscript in addition to the literature review; The final draft of the manuscript was read and approved by all the authors.
Conflict-of-interest statement: The senior author (Basson MD) is co-inventor on patents applied for by the University of North Dakota describing the use of small molecule FAK activators to promote mucosal healing. The authors have no other conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Marc D Basson, MD, PhD, Professor, Department of Biomedical Sciences, University of North Dakota School of Medicine and Health Sciences, 1301 North Columbia Road, Grand Forks, ND 58202, United States. marc.basson@und.edu
Received: October 4, 2021 Peer-review started: October 4, 2021 First decision: December 4, 2021 Revised: December 12, 2021 Accepted: March 25, 2022 Article in press: March 25, 2022 Published online: May 7, 2022
Abstract
The integrity of the gastrointestinal mucosa plays a crucial role in gut homeostasis, which depends upon the balance between mucosal injury by destructive factors and healing via protective factors. The persistence of noxious agents such as acid, pepsin, nonsteroidal anti-inflammatory drugs, or Helicobacter pylori breaks down the mucosal barrier and injury occurs. Depending upon the size and site of the wound, it is healed by complex and overlapping processes involving membrane resealing, cell spreading, purse-string contraction, restitution, differentiation, angiogenesis, and vasculogenesis, each modulated by extracellular regulators. Unfortunately, the gut does not always heal, leading to such pathology as peptic ulcers or inflammatory bowel disease. Currently available therapeutics such as proton pump inhibitors, histamine-2 receptor antagonists, sucralfate, 5-aminosalicylate, antibiotics, corticosteroids, and immunosuppressants all attempt to minimize or reduce injury to the gastrointestinal tract. More recent studies have focused on improving mucosal defense or directly promoting mucosal repair. Many investigations have sought to enhance mucosal defense by stimulating mucus secretion, mucosal blood flow, or tight junction function. Conversely, new attempts to directly promote mucosal repair target proteins that modulate cytoskeleton dynamics such as tubulin, talin, Ehm2, filamin-a, gelsolin, and flightless I or that proteins regulate focal adhesions dynamics such as focal adhesion kinase. This article summarizes the pathobiology of gastrointestinal mucosal healing and reviews potential new therapeutic targets.
Core Tip: The integrity of the gastrointestinal mucosa is crucial in gut homeostasis, which depends upon the balance between mucosal injury by destructive factors and healing via protective factors. An excess of destructive agents breaks down the mucosal barrier. Upon injury, under physiological conditions, gastrointestinal mucosa heals itself by complex processes. However, the gut may not heal under pathological conditions. Currently available drugs attempt to minimize or reduce injury to the gastrointestinal tract. Recent studies have focused on improving mucosal defense or directly promoting mucosal repair. This article summarizes the pathobiology of gastrointestinal mucosal healing and reviews potential new therapeutic targets.
