Heme oxygenase-1 induction contributes to renoprotection by G-CSF during rhabdomyolysis-associated acute kidney injury

Qingqing Wei, William D. Hill, Yunchao Su, Shuang Huang, Zheng Dong

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

Granulocyte colony-stimulating factor (G-CSF) is renoprotective during acute kidney injury (AKI) induced by ischemia and cisplatin nephrotoxicity; however, the underlying mechanism is not entirely clear. Rhabdomyolysis is another important clinical cause of AKI, due to the release of nephrotoxins (e.g., heme) from disrupted muscles. The current study has determined the effects of G-CSF on rhabdomyolysis- associated AKI using in vivo and in vitro models. In C57BL/6 mice, intramuscular injection of glycerol induced AKI, which was partially prevented by G-CSF pretreatment. Consistently, glycerolinduced renal tissue damage was ameliorated by G-CSF. In addition, animal survival following the glycerol injection was improved from ~30 to ~70% by G-CSF. In cultured renal tubular cells, hemininduced apoptosis was also suppressed by G-CSF. Interestingly, G-CSF induced heme oxygenase-1 (HO-1, a critical enzyme for heme/hemin degradation and detoxification) in both cultured tubular cells and mouse kidneys. Blockade of HO-1 with protoporphyrin IX zinc(II) (ZnPP) could largely diminish the protective effects of GCSF. Together, these results demonstrated the renoprotective effects of G-CSF in rhabdomyolysis-associated AKI. Notably, G-CSF may directly protect against tubular cell injury under the disease condition by inducing HO-1.

Original languageEnglish (US)
Pages (from-to)F162-F170
JournalAmerican Journal of Physiology - Renal Physiology
Volume301
Issue number1
DOIs
StatePublished - Jul 2011

Keywords

  • Apoptosis
  • Glycerol-induced rhabdomyolysis
  • Renal tubular cell injury

ASJC Scopus subject areas

  • Physiology
  • Urology

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