Microbiota and Gut Health: Promising Prospects for Clinical Trials from Bench to Bedside

Figure 2

(a) Under the normoxia condition, HIF2α will be hydroxylated by PHDs and FIH, resulting in proteosomal degradation. (b) Under hypoxia condition, enzymatic activity of PHDs and FIH is inhibited during hypoxia, which stabilizes HIF subunits. Once they have been transported to the nucleus, they form a complex with their subunit, pull in p300 and CBP, and then bind to hypoxia-responsive elements (HREs) in the promoters of target genes to start transcription. (c) Hypoxia increases the survival of myeloid cells so that those cells can release more proinflammatory cytokines, such as TNF, which can destroy the tight junction protein of the epithelial layer as well as increase the chance of epithelial cell apoptosis, together increasing the permeability of the gut barrier. Subsequently, epithelial cells under hypoxia conditions are more likely to secrete more cell-adhesion molecules and proinflammatory mediators, attracting more immune cell adhesion and causing inflammation. Additionally, hypoxia condition also can promote the macrophage cells to produce more proangiogenic factor vascular endothelial growth factor A (VEGFA). All the factors attributed to the accumulation of inflammation at the colitis site trigger the onset of IBD.