Megalin in acute kidney injury: foe and friend

Am J Physiol Renal Physiol. 2014 Jan;306(2):F147-54. doi: 10.1152/ajprenal.00378.2013. Epub 2013 Nov 6.

Abstract

The kidney proximal tubule is a key target in many forms of acute kidney injury (AKI). The multiligand receptor megalin is responsible for the normal proximal tubule uptake of filtered molecules, including nephrotoxins, cytokines, and markers of AKI. By mediating the uptake of nephrotoxins, megalin plays an essential role in the development of some types of AKI. However, megalin also mediates the tubular uptake of molecules implicated in the protection against AKI, and changes in megalin expression have been demonstrated in AKI in animal models. Thus, modulation of megalin expression in response to AKI may be an important part of the tubule cell adaption to cellular protection and regeneration and should be further investigated as a potential target of intervention. This review explores current evidence linking megalin expression and function to the development, diagnosis, and progression of AKI as well as renal protection against AKI.

Keywords: acute kidney injury; biomarkers; cisplatin; megalin; nephrotoxins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Kidney Injury / physiopathology*
  • Acute-Phase Proteins / biosynthesis
  • Acute-Phase Proteins / genetics
  • Animals
  • Humans
  • Kidney Tubules / cytology
  • Kidney Tubules / physiology
  • Kidney Tubules / physiopathology
  • Lipocalin-2
  • Lipocalins / biosynthesis
  • Lipocalins / genetics
  • Low Density Lipoprotein Receptor-Related Protein-2 / chemistry
  • Low Density Lipoprotein Receptor-Related Protein-2 / genetics
  • Low Density Lipoprotein Receptor-Related Protein-2 / physiology*
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / genetics
  • Signal Transduction / genetics
  • Signal Transduction / physiology

Substances

  • Acute-Phase Proteins
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Low Density Lipoprotein Receptor-Related Protein-2
  • Proto-Oncogene Proteins