Vascular endothelial growth factor promotes physical wound repair and is anti-apoptotic in primary distal lung epithelial and A549 cells

Jonathan R. Roberts, Gavin D. Perkins, Takeshi Fujisawa, Kerry A. Pettigrew, Fang Gao, Asif Ahmed, David R. Thickett

Research output: Contribution to journalArticle

Abstract

Objective: There is evidence to suggest a beneficial role for growth factors, including vascular endothelial growth factor (VEGF), in tissue repair and proliferation after injury within the lung. Whether this effect is mediated predominantly by actions on endothelial cells or epithelial cells is unknown. This study tested the hypothesis that VEGF acts as an autocrine trophic factor for human adult alveolar epithelial cells and that under situations of pro-apoptotic stress, VEGF reduces cell death.
Design: In vitro cell culture study looking at the effects of 0.03% H2O2 on both A549 and primary distal lung epithelial cells.Measurement and Main Results: Primary adult human distal lung epithelial cells express both the soluble and membrane-associated VEGF isoforms and VEGF receptors 1 and 2. At physiologically relevant doses, soluble VEGF isoforms stimulate wound repair and have a proliferative action. Specific receptor ligands confirmed that this effect was mediated by VEGF receptor 1. In addition to proliferation, we demonstrate that VEGF reduces A549 and distal lung epithelial cell apoptosis when administered after 0.03% H2O2 injury. This effect occurs due to reduced caspase-3 activation and is phosphatidylinositol 3′–kinase dependent.
Conclusion: In addition to its known effects on endothelial cells, VEGF acts as a growth and anti-apoptotic factor on alveolar epithelial cells. VEGF treatment may have potential as a rescue therapy for diseases associated with alveolar epithelial damage such as acute respiratory distress syndrome.
Original languageEnglish
Pages (from-to)2164-2170
Number of pages7
JournalCritical Care Medicine
Volume35
Issue number9
DOIs
Publication statusPublished - Sep 2007

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Vascular Endothelial Growth Factor A
Epithelial Cells
Lung
Wounds and Injuries
Vascular Endothelial Growth Factor Receptor-1
Alveolar Epithelial Cells
Protein Isoforms
Endothelial Cells
Vascular Endothelial Growth Factor Receptor-2
A549 Cells
Adult Respiratory Distress Syndrome
Lung Injury
Phosphatidylinositols
Caspase 3
Intercellular Signaling Peptides and Proteins
Cell Death
Cell Culture Techniques
Apoptosis
Ligands
Membranes

Keywords

  • vascular endothelial growth factor
  • apoptosis
  • acute respiratory distress syndrome
  • epithelium repair

Cite this

Roberts, Jonathan R. ; Perkins, Gavin D. ; Fujisawa, Takeshi ; Pettigrew, Kerry A. ; Gao, Fang ; Ahmed, Asif ; Thickett, David R. / Vascular endothelial growth factor promotes physical wound repair and is anti-apoptotic in primary distal lung epithelial and A549 cells. In: Critical Care Medicine. 2007 ; Vol. 35, No. 9. pp. 2164-2170.
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Vascular endothelial growth factor promotes physical wound repair and is anti-apoptotic in primary distal lung epithelial and A549 cells. / Roberts, Jonathan R.; Perkins, Gavin D.; Fujisawa, Takeshi; Pettigrew, Kerry A.; Gao, Fang; Ahmed, Asif; Thickett, David R.

In: Critical Care Medicine, Vol. 35, No. 9, 09.2007, p. 2164-2170.

Research output: Contribution to journalArticle

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T1 - Vascular endothelial growth factor promotes physical wound repair and is anti-apoptotic in primary distal lung epithelial and A549 cells

AU - Roberts, Jonathan R.

AU - Perkins, Gavin D.

AU - Fujisawa, Takeshi

AU - Pettigrew, Kerry A.

AU - Gao, Fang

AU - Ahmed, Asif

AU - Thickett, David R.

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N2 - Objective: There is evidence to suggest a beneficial role for growth factors, including vascular endothelial growth factor (VEGF), in tissue repair and proliferation after injury within the lung. Whether this effect is mediated predominantly by actions on endothelial cells or epithelial cells is unknown. This study tested the hypothesis that VEGF acts as an autocrine trophic factor for human adult alveolar epithelial cells and that under situations of pro-apoptotic stress, VEGF reduces cell death.Design: In vitro cell culture study looking at the effects of 0.03% H2O2 on both A549 and primary distal lung epithelial cells.Measurement and Main Results: Primary adult human distal lung epithelial cells express both the soluble and membrane-associated VEGF isoforms and VEGF receptors 1 and 2. At physiologically relevant doses, soluble VEGF isoforms stimulate wound repair and have a proliferative action. Specific receptor ligands confirmed that this effect was mediated by VEGF receptor 1. In addition to proliferation, we demonstrate that VEGF reduces A549 and distal lung epithelial cell apoptosis when administered after 0.03% H2O2 injury. This effect occurs due to reduced caspase-3 activation and is phosphatidylinositol 3′–kinase dependent.Conclusion: In addition to its known effects on endothelial cells, VEGF acts as a growth and anti-apoptotic factor on alveolar epithelial cells. VEGF treatment may have potential as a rescue therapy for diseases associated with alveolar epithelial damage such as acute respiratory distress syndrome.

AB - Objective: There is evidence to suggest a beneficial role for growth factors, including vascular endothelial growth factor (VEGF), in tissue repair and proliferation after injury within the lung. Whether this effect is mediated predominantly by actions on endothelial cells or epithelial cells is unknown. This study tested the hypothesis that VEGF acts as an autocrine trophic factor for human adult alveolar epithelial cells and that under situations of pro-apoptotic stress, VEGF reduces cell death.Design: In vitro cell culture study looking at the effects of 0.03% H2O2 on both A549 and primary distal lung epithelial cells.Measurement and Main Results: Primary adult human distal lung epithelial cells express both the soluble and membrane-associated VEGF isoforms and VEGF receptors 1 and 2. At physiologically relevant doses, soluble VEGF isoforms stimulate wound repair and have a proliferative action. Specific receptor ligands confirmed that this effect was mediated by VEGF receptor 1. In addition to proliferation, we demonstrate that VEGF reduces A549 and distal lung epithelial cell apoptosis when administered after 0.03% H2O2 injury. This effect occurs due to reduced caspase-3 activation and is phosphatidylinositol 3′–kinase dependent.Conclusion: In addition to its known effects on endothelial cells, VEGF acts as a growth and anti-apoptotic factor on alveolar epithelial cells. VEGF treatment may have potential as a rescue therapy for diseases associated with alveolar epithelial damage such as acute respiratory distress syndrome.

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