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

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.

• Authors: Yiwen Li, Jianyong Wu, Zhangfei Shou, Qiang He, Ping Zhang, Fei Han, Hen Li, Jianghua Chen
• Journal: Nephrology (Carlton, Vic.) (Nephrology (Carlton)) Vol. 13 Issue 6 Pg. 508-16 (Dec 2008) ISSN: 1440-1797 [Electronic] Australia
• PMID: 18331437 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Animals
• Apoptosis (drug effects)
• Blood Urea Nitrogen
• Cell Proliferation (drug effects)
• Cytokines (biosynthesis)
• Granulocyte Colony-Stimulating Factor (pharmacology, therapeutic use)
• Ischemia (drug therapy)
• Kidney (blood supply, 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)