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

35 Citations (Scopus)

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 1 2011

Fingerprint

Rhabdomyolysis
Heme Oxygenase-1
Granulocyte Colony-Stimulating Factor
Acute Kidney Injury
Heme
Kidney
Glycerol
Hemin
Intramuscular Injections
Inbred C57BL Mouse
Cisplatin
Cultured Cells
Ischemia
Apoptosis
Muscles
Injections
Wounds and Injuries

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Urology

Cite this

Heme oxygenase-1 induction contributes to renoprotection by G-CSF during rhabdomyolysis-associated acute kidney injury. / Wei, Qingqing; Hill, William D.; Su, Yunchao; Huang, Shuang; Dong, Zheng.

In: American Journal of Physiology - Renal Physiology, Vol. 301, No. 1, 01.07.2011, p. F162-F170.

Research output: Contribution to journalArticle

@article{588eed82487841bbafdb1fa47c1f8cd3,
title = "Heme oxygenase-1 induction contributes to renoprotection by G-CSF during rhabdomyolysis-associated acute kidney injury",
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.",
keywords = "Apoptosis, Glycerol-induced rhabdomyolysis, Renal tubular cell injury",
author = "Qingqing Wei and Hill, {William D.} and Yunchao Su and Shuang Huang and Zheng Dong",
year = "2011",
month = "7",
day = "1",
doi = "10.1152/ajprenal.00438.2010",
language = "English (US)",
volume = "301",
pages = "F162--F170",
journal = "American Journal of Physiology - Heart and Circulatory Physiology",
issn = "0363-6135",
publisher = "American Physiological Society",
number = "1",

}

TY - JOUR

T1 - Heme oxygenase-1 induction contributes to renoprotection by G-CSF during rhabdomyolysis-associated acute kidney injury

AU - Wei, Qingqing

AU - Hill, William D.

AU - Su, Yunchao

AU - Huang, Shuang

AU - Dong, Zheng

PY - 2011/7/1

Y1 - 2011/7/1

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Glycerol-induced rhabdomyolysis

KW - Renal tubular cell injury

UR - http://www.scopus.com/inward/record.url?scp=79960054643&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960054643&partnerID=8YFLogxK

U2 - 10.1152/ajprenal.00438.2010

DO - 10.1152/ajprenal.00438.2010

M3 - Article

C2 - 21511696

AN - SCOPUS:79960054643

VL - 301

SP - F162-F170

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

SN - 0363-6135

IS - 1

ER -