Regulated oxygen sensing by protein hydroxylation in renal erythropoietin-producing cells.
The kidney is a major site of systemic oxygen sensing, regulating blood erythrocyte and hence oxygen content by hypoxia-inducible erythropoietin (Epo) expression. A constant ratio between blood perfusion and oxygen consumption, a stable corticomedullary oxygen gradient, and a relatively low tissue Po(2) are the prerequisites for the function of renal Epo-producing and oxygen-sensing (REPOS) cells, which are located in the juxtamedullary cortex. In kidney disease, renal oxygen consumption is decreased, leading to an increase in Po(2), dysfunction of REPOS cells, and anemia. The molecular principles of cellular oxygen sensing have been elucidated in the last few years, and genetically altered mouse models as well as hereditary diseases causing erythrocytosis have clarified the oxygen-signaling cascade leading to increased Epo expression in REPOS cells. However, the consequences of a number of recently discovered factors for the regulation of oxygen signaling in REPOS cells are unclear, asking for novel cell culture models which might be hampered by the putative neuron-like nature of this enigmatic cell type.
Wenger
Roland H
RH
Institute of Physiology and Zürich Center for Integrative Human Physiology ZIHP, University of Zürich, Zürich, Switzerland. roland.wenger@access.uzh.ch
Hoogewijs
David
D
D000740:Anemia / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D004921:Erythropoietin / Q000097:blood / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D006397:Hematinics / Q000627:therapeutic use; D006801:Humans; D006900:Hydroxylation; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D007668:Kidney / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010100:Oxygen / Q000097:blood / Q000378:metabolism*; D010101:Oxygen Consumption; D011086:Polycythemia / Q000378:metabolism / Q000473:pathology; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D012079:Renal Circulation; D015398:Signal Transduction; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
D051792:Basic Helix-Loop-Helix Proteins; D004921:Erythropoietin; D006397:Hematinics; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D064799:Hypoxia-Inducible Factor-Proline Dioxygenases; D010100:Oxygen; D011393:Procollagen-Proline Dioxygenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099162:Endothelial PAS Domain-Containing Protein 1; C490190:EGLN1 protein, human; C497446:VHL protein, human