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Oxygen metabolism and barrier regulation in the intestinal mucosa
Louise E. Glover, … , J. Scott Lee, Sean P. Colgan
Louise E. Glover, … , J. Scott Lee, Sean P. Colgan
Published October 3, 2016; First published August 8, 2016
Citation Information: J Clin Invest. 2016;126(10):3680-3688. https://doi.org/10.1172/JCI84429.
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Category: Review Series

Oxygen metabolism and barrier regulation in the intestinal mucosa

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Abstract

Mucosal surfaces are lined by epithelial cells and provide an important barrier to the flux of antigens from the outside. This barrier is provided at a number of levels, including epithelial junctional complexes, mucus production, and mucosa-derived antimicrobials. Tissue metabolism is central to the maintenance of homeostasis in the mucosa. In the intestine, for example, baseline pO2 levels are uniquely low due to counter-current blood flow and the presence of large numbers of bacteria. As such, hypoxia and HIF signaling predominates normal intestinal metabolism and barrier regulation during both homeostasis and active inflammation. Contributing factors that elicit important adaptive responses within the mucosa include the transcriptional regulation of tight junction proteins, metabolic regulation of barrier components, and changes in autophagic flux. Here, we review recent literature around the topic of hypoxia and barrier function in health and during disease.

Authors

Louise E. Glover, J. Scott Lee, Sean P. Colgan

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Figure 1

Physiologic hypoxia and barrier regulation in the healthy intestinal mucosa.

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Physiologic hypoxia and barrier regulation in the healthy intestinal muc...
(A) Localization of low pO2 along the crypt-villus axis and the presence of “physiologic hypoxia.” Colonic mucosa of healthy mice retain small amounts of nitroimidazole adduct (Hypoxyprobe) that is detected along the luminal aspect of the colon (red). Blue depicts nuclei counterstaining with Dapi. (B) A mechanism in which microbially derived SCFAs, such as butyrate, elicit increased O2 consumption to the extent that HIF is stabilized and transcriptionally active. Also shown here are barrier-related pathways that are directly regulated by HIF. (Cr, creatine; PCr, phosphocreatine; HIF, hypoxia-inducible factor; CK, creatine kinase; CLDN1, claudin-1; ITF, intestinal trefoil factor).
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ISSN: 0021-9738 (print), 1558-8238 (online)

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