Medicine Innovates Medicine Innovates: Delivering innovations in medicine to the world for better health and prosperity
Significance Statement
In recent years, the intestinal mucosa has proven to be an intriguing organ to study tissue oxygenation processes. The highly vascularized lamina propria juxtaposed to an anaerobic lumen containing trillions of metabolically active microbes results in one of the most austere tissue microenvironments in the body. Studies to date have determined that a healthy mucosa contains a steep oxygen gradient along the length of the intestine and from the lumen to the serosa. Advances in technology have allowed multiple independent measures and indicate that in the healthy mucosa is a lesson in contrasts. Breathable air at sea level contains a partial O2 pressure (pO2) of ~145 mmHg (approximately 21% O2). Measurements of the healthy lung alveolus have revealed a pO2 of 100–110 mmHg (8). By stark contrast, the most luminal aspect of the healthy colon exits at a pO2 of less than 10 mm Hg, so called “physiologic hypoxia”. This unique physiology results from a combination of factors including counter-current exchange blood flow, fluctuating oxygen demands, epithelial metabolism, and oxygen diffusion into the lumen. Such conditions result in the activation of a number of hypoxia-related signaling processes, including stabilization of the transcription factor hypoxia-inducible factor (HIF). These studies have shown that these low O2 conditions are critical for the constitutive expression of certain innate immune factors as well as proteins important in the normal maintenance of epithelial barrier function. In this article, we review the principles of mucosal oxygen delivery, metabolism, and endpoint functional responses that result from this unique oxygenation profile.
Figure legend
Staining of normal mouse colon for regions of hypoxia (e.g. pO2<10mm Hg) shown in red using oxygen-sensitive nitroimidazole dyes. Blue staining depicts the staining of cell nuclei.
Journal Reference
Am J Physiol Cell Physiol. 2015 Sep 15;309(6):C350-60.
Zheng L1, Kelly CJ1, Colgan SP2.
[expand title=”Show Affiliations”]1Department of Medicine and Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado.
2Department of Medicine and Mucosal Inflammation Program, University of Colorado School of Medicine, Aurora, Colorado [email protected].
[/expand]Abstract
In recent years, the intestinal mucosa has proven to be an intriguing organ to study tissue oxygenation. The highly vascularized lamina propria juxtaposed to an anaerobic lumen containing trillions of metabolically active microbes results in one of the most austere tissue microenvironments in the body. Studies to date have determined that a healthy mucosa contains a steep oxygen gradient along the length of the intestine and from the lumen to the serosa. Advances in technology have allowed multiple independent measures and indicate that, in the healthy mucosa of the small and large intestine, the lumen-apposed epithelia experience Po2 conditions of <10 mmHg, so-called physiologic hypoxia. This unique physiology results from a combination of factors, including countercurrent exchange blood flow, fluctuating oxygen demands, epithelial metabolism, and oxygen diffusion into the lumen. Such conditions result in the activation of a number of hypoxia-related signaling processes, including stabilization of the transcription factor hypoxia-inducible factor. Here, we review the principles of mucosal oxygen delivery, metabolism, and end-point functional responses that result from this unique oxygenation profile.
Copyright © 2015 the American Physiological Society.
Go To Am J Physiol Cell Physiol.