Vascular endothelial growth factor accelerates compensatory lung growth by increasing the alveolar units

Pediatr Res. 2018 Jun;83(6):1182-1189. doi: 10.1038/pr.2018.41. Epub 2018 Apr 11.

Abstract

BackgroundDeficiency of vascular endothelial growth factor (VEGF) is associated with hypoplastic lung diseases, such as congenital diaphragmatic hernia. Provision of VEGF has been demonstrated to be beneficial in hyperoxia-induced bronchopulmonary dysplasia, and hence could induce lung growth and improve the outcome in hypoplastic lung diseases. We aimed to determine the effects of exogenous VEGF in a rodent model of compensatory lung growth after left pneumonectomy.MethodsEight-to-ten-week-old C57Bl6 male mice underwent left pneumonectomy, followed by daily intra-peritoneal injections of saline or VEGF (0.5 mg/kg). Lung volume measurement, pulmonary function tests, and morphometric analyses were performed on post-operative day (POD) 4 and 10. The pulmonary expression of angiogenic factors was analyzed by quantitative polymerase chain reaction and western blot.ResultsLung volume on POD 4 was higher in the VEGF-treated mice (P=0.03). On morphometric analyses, VEGF increased the parenchymal volume (P=0.001), alveolar volume (P=0.0003), and alveolar number (P<0.0001) on POD 4. The VEGF group displayed higher levels of phosphorylated-VEGFR2/VEGFR2 (P=0.03) and epidermal growth factor (EGF) messenger RNA (P=0.01).ConclusionVEGF accelerated the compensatory lung growth in mice, by increasing the alveolar units. These changes may be mediated by VEGFR2 and EGF-dependent mechanisms.

MeSH terms

  • Animals
  • Bronchopulmonary Dysplasia / metabolism
  • Epidermal Growth Factor / metabolism
  • Hyperoxia / metabolism
  • Lung / growth & development*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neovascularization, Physiologic
  • Organ Size
  • Organogenesis
  • Pneumonectomy
  • Pulmonary Alveoli / growth & development*
  • Vascular Endothelial Growth Factor A / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / metabolism

Substances

  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • Epidermal Growth Factor
  • Kdr protein, mouse
  • Vascular Endothelial Growth Factor Receptor-2