Oxygen sensors as therapeutic targets in kidney disease

Nephrol Ther. 2017 Apr:13 Suppl 1:S29-S34. doi: 10.1016/j.nephro.2017.01.015.

Abstract

Hypoxia is a common clinical problem that has profound effects on renal homeostasis. Prolyl-4-hydroxylases PHD1, 2 and 3 function as oxygen sensors and control the activity of hypoxia-inducible factor (HIF), an oxygen-sensitive transcription factor that regulates a multitude of hypoxia responses, which help cells and tissues to adapt to low oxygen environments. This review provides an overview of the molecular mechanisms that govern these hypoxia responses and discusses clinical experience with compounds that inhibit prolyl-4-hydroxylases to harness HIF responses for therapy in nephrology.

Keywords: Chronic kidney disease; Erythropoietin; Hypoxia; Hypoxia-inducible factor; Prolyl-4-hydroxylase.

Publication types

  • Review

MeSH terms

  • Erythropoietin / biosynthesis
  • Homeostasis / genetics*
  • Humans
  • Hypoxia / metabolism*
  • Hypoxia-Inducible Factor-Proline Dioxygenases / metabolism*
  • Kidney / metabolism*
  • Oxygen / metabolism*
  • Prolyl-Hydroxylase Inhibitors / metabolism*
  • Renal Insufficiency, Chronic / enzymology*
  • Renal Insufficiency, Chronic / metabolism

Substances

  • Prolyl-Hydroxylase Inhibitors
  • Erythropoietin
  • Hypoxia-Inducible Factor-Proline Dioxygenases
  • Oxygen