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


METHODS
In vitro cell culture study looking at the effects of 0.03% H2O2 on both A549 and primary distal lung epithelial cells.


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.


CONCLUSIONS
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.
Roberts
Jonathan R
JR
Lung Injury and Fibrosis Treatment Program, Department of Medical Sciences, The Medical School University of Birmingham, Birmingham, UK.
Perkins
Gavin D
GD
Fujisawa
Takeshi
T
Pettigrew
Kerry A
KA
Gao
Fang
F
Ahmed
Asif
A
Thickett
David R
DR
D000328:Adult; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D008168:Lung / Q000166:cytology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
D042461:Vascular Endothelial Growth Factor A; D040262:Receptors, Vascular Endothelial Growth Factor; D053148:Caspase 3