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
- Research Support, N.I.H., Extramural
- Research Support, Non-U.S. Gov't
- Review
MeSH terms
- Anemia / blood
- Anemia / drug therapy
- Anemia / genetics
- Animals
- Basic Helix-Loop-Helix Transcription Factors / genetics
- Basic Helix-Loop-Helix Transcription Factors / metabolism
- Bone Marrow / metabolism
- Erythrocytes / drug effects
- Erythrocytes / metabolism*
- Erythropoiesis* / drug effects
- Erythropoiesis* / genetics
- Erythropoietin / biosynthesis
- Erythropoietin / blood*
- Erythropoietin / genetics
- Gene Expression Regulation
- Hematinics / therapeutic use
- Homeostasis
- Humans
- Hypoxia / blood*
- Hypoxia / genetics
- Iron / blood*
- Kidney / metabolism
- Oxygen / blood*
- Polycythemia / blood
- Polycythemia / genetics
- Procollagen-Proline Dioxygenase / genetics
- Procollagen-Proline Dioxygenase / metabolism
- Protein Processing, Post-Translational
- Von Hippel-Lindau Tumor Suppressor Protein / blood
- Von Hippel-Lindau Tumor Suppressor Protein / genetics
Substances
- Basic Helix-Loop-Helix Transcription Factors
- Hematinics
- Erythropoietin
- endothelial PAS domain-containing protein 1
- Iron
- Procollagen-Proline Dioxygenase
- Von Hippel-Lindau Tumor Suppressor Protein
- Oxygen