Expression of angiogenic factors and their receptors in postnatal mouse developing lung.
OBJECTIVE
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.
Tsao
Po-Nien
PN
Division of Neonatology, Department of Pediatrics, National Taiwan University Hospital and Taiwan University College of Medicine, Taipei, Taiwan.
Li
Hung
H
Wei
Shu-Chen
SC
Ko
Min-Liang
ML
Chou
Hung-Chieh
HC
Hsieh
Wu-Shiun
WS
Hsieh
Fon-Jou
FJ
D000818:Animals; D000831:Animals, Newborn; D008168:Lung / Q000098:blood supply* / Q000378:metabolism*; D051379:Mice; D018919:Neovascularization, Physiologic / Q000502:physiology*; D000072483:Placenta Growth Factor; D011257:Pregnancy Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
C000608037:Pgf protein, mouse; D011257:Pregnancy Proteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000072483:Placenta Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2