Pretreatment with granulocyte colony-stimulating factor attenuated renal ischaemia and reperfusion injury via activation of PI3/Akt signal pathway

Nephrology (Carlton). 2008 Dec;13(6):508-16. doi: 10.1111/j.1440-1797.2008.00928.x. Epub 2008 Mar 5.

Abstract

Aim: Granulocyte colony-stimulating factor (G-CSF) has been shown to exert protective effects in various tissues and experimental models of ischaemia-induced injury. However, the mechanism of renoprotective action in ischaemia/reperfusion (I/R) renal injury of G-CSF was unknown.

Methods: Male C57BL/6J mice, subjected to renal ischaemia for 45 min, 48 h and 7 days reperfusion, were administered either saline, wortmannin, G-CSF, and G-CSF plus wortmannin 3 days prior to I/R. Saline-treated group served as the control. At 48 h and 7 days of reperfusion, the mice were killed.

Results: Significantly, renal dysfunction and morphological injury were identified at 48 h and 7 days after I/R. Wortmannin pretreatment worsened the renal injury significantly. However, G-CSF pretreatment significantly attenuated renal injury, reduced the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive ratio of renal tubular epithelial cells and inflammation cytokine expression in the kidney. Moreover, G-CSF pretreatment inhibited the expression of Bax and increased the expression of bcl-2 and p-Akt in the kidney. Wortmannin blunted the beneficial effects of G-CSF.

Conclusion: The cytoprotective action of G-CSF against I/R injury seems to be associated with its anti-apoptotic action mediated by upregulation of p-Akt signal pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Blood Urea Nitrogen
  • Cell Proliferation / drug effects
  • Cytokines / biosynthesis
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Granulocyte Colony-Stimulating Factor / therapeutic use*
  • Ischemia / drug therapy*
  • Kidney / blood supply*
  • Kidney / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phosphatidylinositol 3-Kinases / physiology*
  • Proto-Oncogene Proteins c-akt / physiology*
  • Proto-Oncogene Proteins c-bcl-2 / analysis
  • Receptors, Granulocyte Colony-Stimulating Factor / analysis
  • Reperfusion Injury / prevention & control*
  • Signal Transduction / physiology*
  • bcl-2-Associated X Protein / analysis

Substances

  • Cytokines
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Granulocyte Colony-Stimulating Factor
  • bcl-2-Associated X Protein
  • Granulocyte Colony-Stimulating Factor
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt