VEGF expression is downregulated in nitrofen-induced congenital diaphragmatic hernia.
BACKGROUND
Vascular endothelial growth factor (VEGF) is upregulated in pulmonary alveolarization. However, developmental expression of pulmonary VEGF and its possible role in the pathogenesis of CDH are not well described.


METHODS
Timed-pregnant VEGF-LacZ mice, possessing a beta-galactosidase reporter introduced into the 3' region of the VEGF gene, were used to examine fetal lung gene expression in a model of nitrofen-induced CDH.


RESULTS
VEGF gene expression increased from embryonic day 13 until its peak at embryonic day 16 and then decreased until term in all groups. This pattern was most apparent in the periphery with smaller differences noted in central lung locations. Expression of VEGF/beta-gal in the lungs of nitrofen-treated mice was less than controls at all time-points (P <.0001) The type-II pneumocyte population did not significantly differ between the groups. Study concentrations of nitrofen showed no effect on vascular endothelial proliferation in vitro.


CONCLUSIONS
Nitrofen downregulates the production of VEGF during gestation and attenuates the peak seen at the onset of the canalicular stage, despite preservation of type-II pneumocytes. This effect was most pronounced in peripheral lung tissue. The authors speculate that altered VEGF expression may have a pivotal role in the pathogenesis of nitrofen-induced CDH.
Chang
Robert
R
Department of Surgery, Children's Hospital Harvard Medical School, Boston, MA, USA.
Andreoli
Steven
S
Ng
Yin-Shan
YS
Truong
Thanh
T
Smith
Sandra R
SR
Wilson
Jay
J
D'Amore
Patricia A
PA
D000014:Abnormalities, Drug-Induced / Q000196:embryology / Q000378:metabolism; D000015:Abnormalities, Multiple / Q000139:chemically induced / Q000196:embryology; D000818:Animals; D003964:Diaphragm / Q000196:embryology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D005865:Gestational Age; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000378:metabolism*; D065630:Hernias, Diaphragmatic, Congenital; D006579:Heterozygote; D007763:Lac Operon; D051379:Mice; D008822:Mice, Transgenic; D009024:Morphogenesis; D010647:Phenyl Ethers / Q000633:toxicity; D011650:Pulmonary Alveoli / Q000737:chemistry / Q000196:embryology; D037701:Pulmonary Surfactant-Associated Protein B / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
D010647:Phenyl Ethers; D037701:Pulmonary Surfactant-Associated Protein B; D042461:Vascular Endothelial Growth Factor A; C007350:nitrofen