Abstract
The kidney is a highly sensitive oxygen sensor and plays a central role in mediating the hypoxic induction of red blood cell production. Efforts to understand the molecular basis of oxygen-regulated erythropoiesis have led to the identification of erythropoietin (EPO), which is essential for normal erythropoiesis and to the purification of hypoxia-inducible factor (HIF), the transcription factor that regulates EPO synthesis and mediates cellular adaptation to hypoxia. Recent insights into the molecular mechanisms that control and integrate cellular and systemic erythropoiesis-promoting hypoxia responses and their potential as a therapeutic target for the treatment of renal anemia are discussed in this review.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Anemia / blood
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Anemia / drug therapy
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Anemia / genetics
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Animals
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Bone Marrow / metabolism
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Erythrocytes / drug effects
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Erythrocytes / metabolism*
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Erythropoiesis* / drug effects
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Erythropoiesis* / genetics
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Erythropoietin / biosynthesis
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Erythropoietin / blood*
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Erythropoietin / genetics
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Gene Expression Regulation
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Hematinics / therapeutic use
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Homeostasis
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Humans
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Hypoxia / blood*
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Hypoxia / genetics
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Iron / blood*
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Kidney / metabolism
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Oxygen / blood*
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Polycythemia / blood
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Polycythemia / genetics
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Procollagen-Proline Dioxygenase / genetics
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Procollagen-Proline Dioxygenase / metabolism
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Protein Processing, Post-Translational
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Von Hippel-Lindau Tumor Suppressor Protein / blood
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Von Hippel-Lindau Tumor Suppressor Protein / genetics
Substances
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Basic Helix-Loop-Helix Transcription Factors
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Hematinics
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Erythropoietin
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endothelial PAS domain-containing protein 1
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Iron
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Procollagen-Proline Dioxygenase
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Von Hippel-Lindau Tumor Suppressor Protein
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Oxygen