Hypoxic regulation of erythropoiesis and iron metabolism

Am J Physiol Renal Physiol. 2010 Jul;299(1):F1-13. doi: 10.1152/ajprenal.00174.2010. Epub 2010 May 5.

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