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Autophagy and tight junction proteins in the intestine and intestinal diseases
The intestinal epithelium (IE) forms an indispensible barrier and interface between the intestinal interstitium and the luminal environment. The IE regulates water, ion and nutrient transport while providing a barrier against toxins, pathogens (bacteria, fungi and virus) and antigens. The apical int...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
KeAi Publishing
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945941/ https://www.ncbi.nlm.nih.gov/pubmed/29767173 http://dx.doi.org/10.1016/j.aninu.2015.08.014 |
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author | Hu, Chien-An A. Hou, Yongqing Yi, Dan Qiu, Yinsheng Wu, Guoyao Kong, Xiangfeng Yin, Yulong |
author_facet | Hu, Chien-An A. Hou, Yongqing Yi, Dan Qiu, Yinsheng Wu, Guoyao Kong, Xiangfeng Yin, Yulong |
author_sort | Hu, Chien-An A. |
collection | PubMed |
description | The intestinal epithelium (IE) forms an indispensible barrier and interface between the intestinal interstitium and the luminal environment. The IE regulates water, ion and nutrient transport while providing a barrier against toxins, pathogens (bacteria, fungi and virus) and antigens. The apical intercellular tight junctions (TJ) are responsible for the paracellular barrier function and regulate trans-epithelial flux of ions and solutes between adjacent cells. Increased intestinal permeability caused by defects in the IE TJ barrier is considered an important pathogenic factor for the development of intestinal inflammation, diarrhea and malnutrition in humans and animals. In fact, defects in the IE TJ barrier allow increased antigenic penetration, resulting in an amplified inflammatory response in inflammatory bowel disease (IBD), necrotizing enterocolitis and ischemia-reperfusion injury. Conversely, the beneficial enhancement of the intestinal TJ barrier has been shown to resolve intestinal inflammation and apoptosis in both animal models of IBD and human IBD. Autophagy (self-eating mechanism) is an intracellular lysosome-dependent degradation and recycling pathway essential for cell survival and homeostasis. Dysregulated autophagy has been shown to be directly associated with many pathological processes, including IBD. Importantly, the crosstalk between IE TJ and autophagy has been revealed recently. We showed that autophagy enhanced IE TJ barrier function by increasing transepithelial resistance and reducing the paracellular permeability of small solutes and ions, which is, in part, by targeting claudin-2, a cation-selective, pore-forming, transmembrane TJ protein, for lysosome (autophagy)-mediated degradation. Interestingly, previous studies have shown that the inflamed intestinal mucosa in patients with active IBD has increased claudin-2 expression. In addition, inflammatory cytokines (for example, tumor necrosis factor-α, interleukin-6, interleukin-13, and interleukin-17) whose levels are increased in IBD patients cause an increase in claudin-2 expression and a claudin-2-dependent increase in TJ permeability. Thus, the role of claudin-2 in intestinal pathological processes has been attributed, in part, to the increase of intestinal TJ permeability. Claudin-2 represents a new therapeutic target in treating IBD, diarrhea and malnutrition in animals and humans. |
format | Online Article Text |
id | pubmed-5945941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | KeAi Publishing |
record_format | MEDLINE/PubMed |
spelling | pubmed-59459412018-05-14 Autophagy and tight junction proteins in the intestine and intestinal diseases Hu, Chien-An A. Hou, Yongqing Yi, Dan Qiu, Yinsheng Wu, Guoyao Kong, Xiangfeng Yin, Yulong Anim Nutr The Sustainable Development of Animal Nutrition and Feeding Environment Forum The intestinal epithelium (IE) forms an indispensible barrier and interface between the intestinal interstitium and the luminal environment. The IE regulates water, ion and nutrient transport while providing a barrier against toxins, pathogens (bacteria, fungi and virus) and antigens. The apical intercellular tight junctions (TJ) are responsible for the paracellular barrier function and regulate trans-epithelial flux of ions and solutes between adjacent cells. Increased intestinal permeability caused by defects in the IE TJ barrier is considered an important pathogenic factor for the development of intestinal inflammation, diarrhea and malnutrition in humans and animals. In fact, defects in the IE TJ barrier allow increased antigenic penetration, resulting in an amplified inflammatory response in inflammatory bowel disease (IBD), necrotizing enterocolitis and ischemia-reperfusion injury. Conversely, the beneficial enhancement of the intestinal TJ barrier has been shown to resolve intestinal inflammation and apoptosis in both animal models of IBD and human IBD. Autophagy (self-eating mechanism) is an intracellular lysosome-dependent degradation and recycling pathway essential for cell survival and homeostasis. Dysregulated autophagy has been shown to be directly associated with many pathological processes, including IBD. Importantly, the crosstalk between IE TJ and autophagy has been revealed recently. We showed that autophagy enhanced IE TJ barrier function by increasing transepithelial resistance and reducing the paracellular permeability of small solutes and ions, which is, in part, by targeting claudin-2, a cation-selective, pore-forming, transmembrane TJ protein, for lysosome (autophagy)-mediated degradation. Interestingly, previous studies have shown that the inflamed intestinal mucosa in patients with active IBD has increased claudin-2 expression. In addition, inflammatory cytokines (for example, tumor necrosis factor-α, interleukin-6, interleukin-13, and interleukin-17) whose levels are increased in IBD patients cause an increase in claudin-2 expression and a claudin-2-dependent increase in TJ permeability. Thus, the role of claudin-2 in intestinal pathological processes has been attributed, in part, to the increase of intestinal TJ permeability. Claudin-2 represents a new therapeutic target in treating IBD, diarrhea and malnutrition in animals and humans. KeAi Publishing 2015-09 2015-09-01 /pmc/articles/PMC5945941/ /pubmed/29767173 http://dx.doi.org/10.1016/j.aninu.2015.08.014 Text en © 2015 Chinese Association of Animal Science and Veterinary Medicine. Production and hosting by Elsevier B.V. on behalf of KeAi Communications Co., Ltd. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | The Sustainable Development of Animal Nutrition and Feeding Environment Forum Hu, Chien-An A. Hou, Yongqing Yi, Dan Qiu, Yinsheng Wu, Guoyao Kong, Xiangfeng Yin, Yulong Autophagy and tight junction proteins in the intestine and intestinal diseases |
title | Autophagy and tight junction proteins in the intestine and intestinal diseases |
title_full | Autophagy and tight junction proteins in the intestine and intestinal diseases |
title_fullStr | Autophagy and tight junction proteins in the intestine and intestinal diseases |
title_full_unstemmed | Autophagy and tight junction proteins in the intestine and intestinal diseases |
title_short | Autophagy and tight junction proteins in the intestine and intestinal diseases |
title_sort | autophagy and tight junction proteins in the intestine and intestinal diseases |
topic | The Sustainable Development of Animal Nutrition and Feeding Environment Forum |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5945941/ https://www.ncbi.nlm.nih.gov/pubmed/29767173 http://dx.doi.org/10.1016/j.aninu.2015.08.014 |
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