The role of hypoxia and Morg1 in renal injury

Eur J Clin Invest. 2015 Mar;45(3):294-302. doi: 10.1111/eci.12405. Epub 2015 Feb 14.

Abstract

Background: Renal hypoxia is known to play an important role in the pathophysiology of acute renal injury as well as in chronic kidney diseases. The mediators of hypoxia are the transcription factors HIF (hypoxia-inducible factors), that are highly regulated. Under normoxic conditions constitutively expressed HIF-α subunits are hydroxylated by prolyl hydroxylases (PHD1, PHD2, and PHD3) and subsequently degraded by proteasomes.

Materials and methods: This narrative review is based on the material searched for and obtained via PubMed and MEDLINE up to January 2015.

Results: The MAPK organizer 1 (Morg1) has been identified to act as a scaffold protein of PHD3 and suppression of Morg1 leads to the stabilization of HIF-α, which forms in the absence of oxygen a heterodimer with HIF-β, translocates to the nucleus and promotes the transcription of HIF target genes.

Conclusions: This review summarizes the current knowledge regarding the role of hypoxia, HIF signalling, and Morg1 in acute and chronic renal injury.

Keywords: Morg1; acute kidney injury; chronic kidney disease (CKD); hypoxia; hypoxia-inducible factor.

Publication types

  • Review

MeSH terms

  • Acute Kidney Injury / etiology*
  • Adaptor Proteins, Signal Transducing / physiology*
  • Aryl Hydrocarbon Receptor Nuclear Translocator / physiology
  • Erythropoietin / physiology
  • Humans
  • Hypoxia / complications*
  • Hypoxia-Inducible Factor 1, alpha Subunit / physiology
  • Kidney Failure, Chronic / etiology
  • Signal Transduction / physiology

Substances

  • Adaptor Proteins, Signal Transducing
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • WDR83 protein, human
  • Erythropoietin
  • Aryl Hydrocarbon Receptor Nuclear Translocator