Louise E. Glover, Sean P. Colgan Gastroenterology

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Presentation transcript:

Hypoxia and Metabolic Factors That Influence Inflammatory Bowel Disease Pathogenesis Louise E. Glover, Sean P. Colgan Gastroenterology Volume 140, Issue 6, Pages 1748-1755 (May 2011) DOI: 10.1053/j.gastro.2011.01.056 Copyright © 2011 AGA Institute Terms and Conditions

Figure 1 Contributions of inflammation and hypoxia to angiogenesis. Inflammation and hypoxia each contribute to angiogenesis during pathogenesis of IBD, partly by induction of vascular endothelial growth factor (VEGF)-A expression in multiple cell types that include submucosal fibroblasts, macrophages, neutrophils (PMNs), and endothelial cells. VEGF-A–induced angiogenesis is likely to be pathogenic and result in abnormal vessel formation and poorly functioning vasculature. Gastroenterology 2011 140, 1748-1755DOI: (10.1053/j.gastro.2011.01.056) Copyright © 2011 AGA Institute Terms and Conditions

Figure 2 Functional features of HIF and mechanism of HIF stabilization. HIF is hydroxylated by the combination of α-ketoglutarate (αKG), molecular oxygen (O2), and the PHD enzymes in normoxic conditions. When O2 becomes limiting (hypoxia), the HIF α subunit is stabilized and binds to the HIF-1 β subunit in the nucleus; the complex binds to the HRE in target genes to regulate their transcription. Gastroenterology 2011 140, 1748-1755DOI: (10.1053/j.gastro.2011.01.056) Copyright © 2011 AGA Institute Terms and Conditions

Gastroenterology 2011 140, 1748-1755DOI: (10. 1053/j. gastro. 2011. 01 Copyright © 2011 AGA Institute Terms and Conditions

Gastroenterology 2011 140, 1748-1755DOI: (10. 1053/j. gastro. 2011. 01 Copyright © 2011 AGA Institute Terms and Conditions