Overexpression of stanniocalcin-1 inhibits reactive oxygen species and renal ischemia/reperfusion injury in mice

Kidney Int. 2012 Oct;82(8):867-77. doi: 10.1038/ki.2012.223. Epub 2012 Jun 13.


Reactive oxygen species, endothelial dysfunction, inflammation, and mitogen-activated protein kinases have important roles in the pathogenesis of ischemia/reperfusion kidney injury. Stanniocalcin-1 (STC1) suppresses superoxide generation in many systems through the induction of mitochondrial uncoupling proteins and blocks the cytokine-induced rise in endothelial permeability. Here we tested whether transgenic overexpression of STC1 protects from bilateral ischemia/reperfusion kidney injury. This injury in wild-type mice caused a halving of the creatinine clearance; severe tubular vacuolization and cast formation; increased infiltration of macrophages and T cells; higher vascular permeability; greater production of superoxide and hydrogen peroxide; and higher ratio of activated extracellular regulated kinase/activated Jun-N-terminal kinase and p38, all compared to sham-treated controls. Mice transgenic for human STC1 expression, however, had resistance to equivalent ischemia/reperfusion injury indicated as no significant change from controls in any of these parameters. Tubular epithelial cells in transgenic mice expressed higher mitochondrial uncoupling protein 2 and lower superoxide generation. Pre-treatment of transgenic mice with paraquat, a generator of reactive oxygen species, before injury restored the susceptibility to ischemia/reperfusion kidney injury, suggesting that STC1 protects by an anti-oxidant mechanism. Thus, STC1 may be a therapeutic target for ischemia/reperfusion kidney injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Kidney Injury / pathology
  • Acute Kidney Injury / physiopathology
  • Acute Kidney Injury / prevention & control*
  • Animals
  • Capillary Permeability
  • Female
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Ion Channels / metabolism
  • Kidney / blood supply
  • Kidney / injuries
  • Kidney / physiopathology
  • MAP Kinase Signaling System
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitochondrial Proteins / metabolism
  • Oxidative Stress
  • Paraquat / toxicity
  • Reactive Oxygen Species / metabolism
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • T-Lymphocytes / pathology
  • Uncoupling Protein 2
  • Up-Regulation


  • Glycoproteins
  • Ion Channels
  • Mitochondrial Proteins
  • Reactive Oxygen Species
  • Recombinant Proteins
  • UCP2 protein, human
  • Ucp2 protein, mouse
  • Uncoupling Protein 2
  • teleocalcin
  • Paraquat