Department of Medicine and the Mucosal Inflammation Program, University of Colorado Denver, RC2 Room 10450, 12700 E. 19th Ave, Aurora, CO, 80045, USA.
J Mol Med (Berl). 2017 Sep;95(9):905-913. doi: 10.1007/s00109-017-1544-2. Epub 2017 May 20.
The intestinal mucosa provides a selective barrier between the anaerobic lumen and a highly metabolic lamina propria. A number of recent studies indicate that acute inflammation of the mucosa can result in tissue hypoxia and associated shifts in tissue metabolism. The activation of hypoxia-inducible factor (HIF) under these conditions has been demonstrated to function as an endogenous molecular cue to promote resolution of inflammation, particularly through the orchestration of barrier repair toward homeostasis. Given the central role of oxygen in tissue metabolism, ongoing studies have defined metabolic endpoints of HIF stabilization as important biomarkers of disease activity. Such findings make HIF and HIF-associated metabolic pathways particularly attractive therapeutic targets in inflammatory bowel disease (IBD). Here, we review the recent literature related to tissue metabolism in IBD.
肠黏膜在厌氧腔和高代谢固有层之间提供了一个选择性屏障。最近的一些研究表明,黏膜的急性炎症可导致组织缺氧和相关的组织代谢改变。在这些条件下,缺氧诱导因子 (HIF) 的激活已被证明是一种内源性分子信号,可促进炎症的消退,特别是通过协调屏障修复以达到体内平衡。鉴于氧气在组织代谢中的核心作用,正在进行的研究已经将 HIF 稳定的代谢终点定义为疾病活动的重要生物标志物。这些发现使得 HIF 和 HIF 相关的代谢途径成为炎症性肠病 (IBD) 治疗的极具吸引力的靶点。在这里,我们回顾了与 IBD 组织代谢相关的最新文献。