title: Role of Intestinal HIF-2α in Health and Disease.
abstract: The intestine is supported by a complex vascular system that undergoes dynamic and transient daily shifts in blood perfusion, depending on the metabolic state. Moreover, the intestinal villi have a steep oxygen gradient from the hypoxic epithelium adjacent to the anoxic lumen to the relative higher tissue oxygenation at the base of villi. Due to the daily changes in tissue oxygen levels in the intestine, the hypoxic transcription factors hypoxia-inducible factor (HIF)-1α and HIF-2α are essential in maintaining intestinal homeostasis. HIF-2α is essential in maintaining proper micronutrient balance, the inflammatory response, and the regenerative and proliferative capacity of the intestine following an acute injury. However, chronic activation of HIF-2α leads to enhanced proinflammatory response, intestinal injury, and colorectal cancer. In this review, we detail the major mechanisms by which HIF-2α contributes to health and disease of the intestine and the therapeutic implications of targeting HIF-2α in intestinal diseases.
authors.affiliation: Department of Molecular & Integrative Physiology and.
authors.forename: Sadeesh K
authors.initials: SK
authors.lastname: Ramakrishnan
authors.affiliation: Department of Molecular & Integrative Physiology and.|Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109; email: shahy@umich.edu.
authors.forename: Yatrik M
authors.initials: YM
authors.lastname: Shah
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D007410:Intestinal Diseases / Q000378:metabolism* / Q000473:pathology*; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000502:physiology*; D010100:Oxygen / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D010100:Oxygen; D000099162:Endothelial PAS Domain-Containing Protein 1
keywords: Crohn's disease; colon cancer; hypoxia; inflammatory bowel disease; iron; ulcerative colitis