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The role of hypoxia in intestinal inflammation
Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the intestine. IBD is a multifactorial disorder, and IBD-associated genes are critical in innate immune response, inflammatory response, autophagy, and epithelial barrier integrity. Moreover, epithelial oxygen tension pl...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2016
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728161/ https://www.ncbi.nlm.nih.gov/pubmed/26812949 http://dx.doi.org/10.1186/s40348-016-0030-1 |
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author | Shah, Yatrik M. |
author_facet | Shah, Yatrik M. |
author_sort | Shah, Yatrik M. |
collection | PubMed |
description | Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the intestine. IBD is a multifactorial disorder, and IBD-associated genes are critical in innate immune response, inflammatory response, autophagy, and epithelial barrier integrity. Moreover, epithelial oxygen tension plays a critical role in intestinal inflammation and resolution in IBD. The intestines have a dynamic and rapid fluctuation in cellular oxygen tension, which is dysregulated in IBD. Intestinal epithelial cells have a steep oxygen gradient where the tips of the villi are hypoxic and the oxygenation increases at the base of the villi. IBD results in heightened hypoxia throughout the mucosa. Hypoxia signals through a well-conserved family of transcription factors, where hypoxia-inducible factor (HIF)-1α and HIF-2α are essential in maintaining intestinal homeostasis. In inflamed mucosa, HIF-1α increases barrier protective genes, elicits protective innate immune responses, and activates an antimicrobial response through the increase in β-defensins. HIF-2α is essential in maintaining an epithelial-elicited inflammatory response and the regenerative and proliferative capacity of the intestine following an acute injury. HIF-1α activation in colitis leads to a protective response, whereas chronic activation of HIF-2α increases the pro-inflammatory response, intestinal injury, and cancer. In this mini-review, we detail the role of HIF-1α and HIF-2α in intestinal inflammation and injury and therapeutic implications of targeting HIF signaling in IBD. |
format | Online Article Text |
id | pubmed-4728161 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-47281612016-02-03 The role of hypoxia in intestinal inflammation Shah, Yatrik M. Mol Cell Pediatr Mini Review Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disease of the intestine. IBD is a multifactorial disorder, and IBD-associated genes are critical in innate immune response, inflammatory response, autophagy, and epithelial barrier integrity. Moreover, epithelial oxygen tension plays a critical role in intestinal inflammation and resolution in IBD. The intestines have a dynamic and rapid fluctuation in cellular oxygen tension, which is dysregulated in IBD. Intestinal epithelial cells have a steep oxygen gradient where the tips of the villi are hypoxic and the oxygenation increases at the base of the villi. IBD results in heightened hypoxia throughout the mucosa. Hypoxia signals through a well-conserved family of transcription factors, where hypoxia-inducible factor (HIF)-1α and HIF-2α are essential in maintaining intestinal homeostasis. In inflamed mucosa, HIF-1α increases barrier protective genes, elicits protective innate immune responses, and activates an antimicrobial response through the increase in β-defensins. HIF-2α is essential in maintaining an epithelial-elicited inflammatory response and the regenerative and proliferative capacity of the intestine following an acute injury. HIF-1α activation in colitis leads to a protective response, whereas chronic activation of HIF-2α increases the pro-inflammatory response, intestinal injury, and cancer. In this mini-review, we detail the role of HIF-1α and HIF-2α in intestinal inflammation and injury and therapeutic implications of targeting HIF signaling in IBD. Springer Berlin Heidelberg 2016-01-26 /pmc/articles/PMC4728161/ /pubmed/26812949 http://dx.doi.org/10.1186/s40348-016-0030-1 Text en © Shah. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
spellingShingle | Mini Review Shah, Yatrik M. The role of hypoxia in intestinal inflammation |
title | The role of hypoxia in intestinal inflammation |
title_full | The role of hypoxia in intestinal inflammation |
title_fullStr | The role of hypoxia in intestinal inflammation |
title_full_unstemmed | The role of hypoxia in intestinal inflammation |
title_short | The role of hypoxia in intestinal inflammation |
title_sort | role of hypoxia in intestinal inflammation |
topic | Mini Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728161/ https://www.ncbi.nlm.nih.gov/pubmed/26812949 http://dx.doi.org/10.1186/s40348-016-0030-1 |
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