title: The early responses of VEGF and its receptors during acute lung injury: implication of VEGF in alveolar epithelial cell survival.
abstract: BACKGROUND
  The function of the vascular endothelial growth factor (VEGF) system in acute lung injury (ALI) is controversial. We hypothesized that the role of VEGF in ALI may depend upon the stages of pathogenesis of ALI.
  
  
  METHODS
  To determine the responses of VEGF and its receptors during the early onset of ALI, C57BL6 mice were subjected to intestinal ischemia or sham operation for 30 minutes followed by intestinal ischemia-reperfusion (IIR) for four hours under low tidal volume ventilation with 100% oxygen. The severity of lung injury, expression of VEGF and its receptors were assessed. To further determine the role of VEGF and its type I receptor in lung epithelial cell survival, human lung epithelial A549 cells were treated with small interference RNA (siRNA) to selectively silence related genes.
  
  
  RESULTS
  IIR-induced ALI featured interstitial inflammation, enhancement of pulmonary vascular permeability, increase of total cells and neutrophils in the bronchoalveolar lavage (BAL), and alveolar epithelial cell death. In the BAL, VEGF was significantly increased in both sham and IIR groups, while the VEGF and VEGF receptor (VEGFR)-1 in the lung tissues were significantly reduced in these two groups. The increase of VEGF in the BAL was correlated with the total protein concentration and cell count. Significant negative correlations were observed between the number of VEGF or VEGFR-1 positive cells, and epithelial cells undergoing cell death. When human lung epithelial A549 cells were pre-treated with 50 nM of siRNA either against VEGF or VEGFR-1 for 24 hours, reduced VEGF and VEGFR-1 levels were associated with reduced cell viability.
  
  
  CONCLUSIONS
  These results suggest that VEGF may have dual roles in ALI: early release of VEGF may increase pulmonary vascular permeability; reduced expression of VEGF and VEGFR-1 in lung tissue may contribute to the death of alveolar epithelial cells.
authors.affiliation: Thoracic Surgery Research Laboratories, Toronto General Research Institute, University Health Network, Toronto, Canada M5G 2C4.
authors.forename: Marco
authors.initials: M
authors.lastname: Mura
authors.forename: Bing
authors.initials: B
authors.lastname: Han
authors.forename: Cristiano F
authors.initials: CF
authors.lastname: Andrade
authors.forename: Rashmi
authors.initials: R
authors.lastname: Seth
authors.forename: David
authors.initials: D
authors.lastname: Hwang
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Waddell
authors.forename: Shaf
authors.initials: S
authors.lastname: Keshavjee
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000378:metabolism* / Q000473:pathology; D040262:Receptors, Vascular Endothelial Growth Factor / Q000096:biosynthesis / Q000502:physiology*; D012128:Respiratory Distress Syndrome / Q000378:metabolism* / Q000473:pathology; D020545:Respiratory Mucosa / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*
chemical_list: D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor