Background and purpose: Several lines of evidence suggest that angiogenesis is necessary for alveolarization and that inhibition of vascular growth during a critical period of early growth may impair alveolarization. However, little is known about the role of angiogenic factors during alveolarization. This study investigated the expression patterns of the Ang-Tie-2 family of endothelium-specific receptor tyrosine kinases and vascular endothelial growth factors and their receptors (VEGF-VEGFR system) during postnatal mouse lung development.
Methods: The lungs from 3 or 4 mice from groups aged 3, 7, 10 and 14 days and adults were removed and dissected from the main bronchi for reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Semi-quantitative RT-PCR of mouse lung total RNA was used to measure the expression levels of these angiogenic factors and their receptors.
Results: During alveolarization, VEGF/Flk-1, Ang-1, Ang-2, and Tie-2 were up-regulated and PlGF/Flt-1 was kept at a relatively constant level. After alveolarization was completed, PlGF was down-regulated, Flt-1 was up-regulated, and VEGF/Flk-1, Ang-1, Ang-2, and Tie-2 were maintained at relatively high levels.
Conclusions: During alveolarization, in mice, VEGF/Flk-1, Ang-1, Ang-2, and Tie-2 are up-regulated and PlGF/ Flt-1 is kept at relatively constant level to promote pulmonary microvascular development. In the adult mouse lung, when most of the vascular network is complete, PlGF is down-regulated and Flt-1 is up-regulated to stop angiogenesis and VEGF/Flk-1, Ang-1, Ang-2 and Tie-2 are kept at relatively high levels to maintain mature pulmonary microvasculature.