VEGF, Bcl-2 and Bad regulated by angiopoietin-1 in oleic acid induced acute lung injury

Qiang Guo, Jun Jin, Jason X.J. Yuan, Amy Zeifman, Jiwan chen, Bo Shen, Jianan Huang

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Molecular mechanisms of acute lung injury (ALI) are poorly defined. Our previous study demonstrated that recombinant angiopoietin-1 (Ang1) can protect against oleic acid (OA) induced ALI at an early stage. The purpose of this study was to elucidate whether vascular endothelial growth factor (VEGF), Bcl-2, and Bad, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) play any role in the protective mechanism of recombinant Ang1 in OA-induced ALI. All BALB/C mice were administered a single dose of OA to induce lung injury. Lungs, bronchoalveolar lavage fluid (BALF), and serum were harvested at certain time points. The expression of VEGF, Bcl-2, Bad, PI3K/Akt, and the histological changes in the lung, and the levels of VEGF, IL-6, and IL-10 in serum and BALF were examined. A second cohort of mice was followed for survival for 7. days. We observed increased expression of VEGF in BALF and serum and reduced expression of VEGF in lung tissue. Recombinant Ang1 treatment, however, up-regulated VEGF expression and p-Akt/Akt in lung tissue but down-regulated VEGF expression in BALF and serum. OA led to a decrease of anti-apoptotic marker Bcl-2 and a marked increase of pro-apoptotic marker Bad. Compared with the ALI group, in the recombinant Ang1 treated group, Bcl-2 expression was restored, and Bad expression was clearly attenuated. In addition, recombinant Ang1 attenuated the lung pathological changes and improved the survival of mice. These findings suggest that recombinant Ang1 may be a promising potential treatment for ALI. It seems that VEGF is mediated by PI3K/Akt pathway which is required for Ang1-mediated protection of lung injury. Activation of Akt stimulates expression of Bcl-2 and inhibits the expression of Bad, thus inhibiting the execution of apoptosis.

Original languageEnglish (US)
Pages (from-to)630-636
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume413
Issue number4
DOIs
StatePublished - Oct 7 2011
Externally publishedYes

Keywords

  • Acute lung injury
  • Bad
  • Bcl-2
  • IL-10
  • IL-6
  • Lung
  • Mice
  • PI3K/Akt
  • VEGF

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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