Heme Oxygenase 1 as a Therapeutic Target in Acute Kidney Injury

Am J Kidney Dis. 2017 Apr;69(4):531-545. doi: 10.1053/j.ajkd.2016.10.037. Epub 2017 Jan 27.

Abstract

A common clinical condition, acute kidney injury (AKI) significantly influences morbidity and mortality, particularly in critically ill patients. The pathophysiology of AKI is complex and involves multiple pathways, including inflammation, autophagy, cell-cycle progression, and oxidative stress. Recent evidence suggests that a single insult to the kidney significantly enhances the propensity to develop chronic kidney disease. Therefore, the generation of effective therapies against AKI is timely. In this context, the cytoprotective effects of heme oxygenase 1 (HO-1) in animal models of AKI are well documented. HO-1 modulates oxidative stress, autophagy, and inflammation and regulates the progression of cell cycle via direct and indirect mechanisms. These beneficial effects of HO-1 induction during AKI are mediated in part by the by-products of the HO reaction (iron, carbon monoxide, and bile pigments). This review highlights recent advances in the molecular mechanisms of HO-1-mediated cytoprotection and discusses the translational potential of HO-1 induction in AKI.

Keywords: Acute kidney injury (AKI); HMOX1; autophagic response; biomarker; cell cycle regulation; cytoprotection; heme oxygenase 1 (HO-1); inflammation; oxidative stress; pathophysiology; renal failure; review; translational research.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Accidents, Occupational
  • Acute Kidney Injury / blood*
  • Acute Kidney Injury / therapy*
  • Adult
  • Autophagy / physiology
  • Cell Cycle Checkpoints / physiology
  • Enzyme Induction / physiology
  • Heme Oxygenase-1 / blood*
  • Heme Oxygenase-1 / physiology
  • Humans
  • Inflammation / blood
  • Inflammation / therapy
  • Leg Injuries / complications
  • Male
  • Oxidative Stress / physiology
  • Rhabdomyolysis / blood
  • Rhabdomyolysis / therapy
  • Translational Medical Research

Substances

  • HMOX1 protein, human
  • Heme Oxygenase-1