Endothelial STAT3 is essential for the protective effects of HO-1 in oxidant-induced lung injury

Xuchen Zhang, Peiying Shan, Ge Jiang, Samuel S M Zhang, Leo E. Otterbein, Xin Yuan Fu, Patty J. Lee

Research output: Contribution to journalArticle

73 Citations (Scopus)

Abstract

Administering high levels of inspired oxygen, or hyperoxia, is commonly used as a life-sustaining measure in critically ill patients. Unfortunately, the oxidant stress generated by prolonged hyperoxia can lead to respiratory failure, multiorgan failure, and death. Although the endothelial cell is known to be a target for hyperoxia-induced injury, its precise role is unclear. Heme oxygenase-1 (HO-1) and "signal transducer and activator of transcription 3" (STAT3) have been found to confer protection against endothelial cell injury. We sought to elucidate the specific roles of HO-1 and STAT3 in hyperoxic lung and endothelial cell injury. Mice or murine lung endothelial cells (MLEC) administered HO-1 siRNA exhibited marked injury and death compared with nonspecific siRNA. Overexpression of either HO-1 or STAT3 confers protection. However, HO-1 and its reaction product carbon monoxide (CO) lose their protective effects in the presence of STAT3 siRNA in MLEC or in endothelial-specific, STAT3-deficient mice. STAT3 overexpression is able to partially rescue HO-1-deficient MLEC from hyperoxia-induced cell death. Our results demonstrate 1) the importance of the endothelium in lethal hyperoxic injury, 2) HO-1 and CO require endothelial STAT3 for their protective effects, and 3) STAT3 confers endothelial cell protection via both HO-1-dependent and independent mechanisms.

Original languageEnglish (US)
JournalFASEB Journal
Volume20
Issue number12
DOIs
StatePublished - Oct 2006
Externally publishedYes

Fingerprint

heme oxygenase (biliverdin-producing)
STAT3 Transcription Factor
Heme Oxygenase-1
Lung Injury
Oxidants
Endothelial cells
oxidants
protective effect
endothelial cells
lungs
Endothelial Cells
hyperoxia
Hyperoxia
small interfering RNA
Small Interfering RNA
mice
Wounds and Injuries
Lung
carbon monoxide
Carbon Monoxide

Keywords

  • Oxygen
  • Signal transduction

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Zhang, X., Shan, P., Jiang, G., Zhang, S. S. M., Otterbein, L. E., Fu, X. Y., & Lee, P. J. (2006). Endothelial STAT3 is essential for the protective effects of HO-1 in oxidant-induced lung injury. FASEB Journal, 20(12). https://doi.org/10.1096/fj.06-5668fje

Endothelial STAT3 is essential for the protective effects of HO-1 in oxidant-induced lung injury. / Zhang, Xuchen; Shan, Peiying; Jiang, Ge; Zhang, Samuel S M; Otterbein, Leo E.; Fu, Xin Yuan; Lee, Patty J.

In: FASEB Journal, Vol. 20, No. 12, 10.2006.

Research output: Contribution to journalArticle

Zhang, X, Shan, P, Jiang, G, Zhang, SSM, Otterbein, LE, Fu, XY & Lee, PJ 2006, 'Endothelial STAT3 is essential for the protective effects of HO-1 in oxidant-induced lung injury', FASEB Journal, vol. 20, no. 12. https://doi.org/10.1096/fj.06-5668fje
Zhang, Xuchen ; Shan, Peiying ; Jiang, Ge ; Zhang, Samuel S M ; Otterbein, Leo E. ; Fu, Xin Yuan ; Lee, Patty J. / Endothelial STAT3 is essential for the protective effects of HO-1 in oxidant-induced lung injury. In: FASEB Journal. 2006 ; Vol. 20, No. 12.
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