PMID:11066091

Citation	Healy, AM, Morgenthau, L, Zhu, X, Farber, HW and Cardoso, WV (2000) VEGF is deposited in the subepithelial matrix at the leading edge of branching airways and stimulates neovascularization in the murine embryonic lung. Dev. Dyn. 219:341-52
Abstract	We used whole lung cultures as a model to study blood vessel formation in vitro and to examine the role that epithelial-mesenchymal interactions play during embryonic pulmonary vascular development. Mouse lungs were isolated at embryonic day 11.5 (E11.5) and cultured for up to 4 days prior to blood vessel analysis. Platelet endothelial cell adhesion molecule-1 (PECAM/CD31) and thrombomodulin (TM/CD141) immunolocalization demonstrate that vascular development occurs in lung cultures. The vascular structures identified in lung cultures first appear as a loosely associated plexus of capillary-like structures that with time surround the airways. To investigate the potential role of vascular endothelial cell growth factor (VEGF) during pulmonary neovascularization, we immunolocalized VEGF in embryonic lungs. Our data demonstrate that VEGF is uniformly present in the airway epithelium and the subepithelial matrix of E11.5 lungs. At later time points, E13.5 and E15.5, VEGF is no longer detected in the proximal airways, but is restricted to the branching tips of airways in the distal lung. RT-PCR analysis reveals that VEGF(164) is the predominant isoform expressed in lung cultures. Grafting heparin-bound VEGF(164) beads onto lung explants locally stimulates a marked neovascular response within 48 hr in culture. Semi-quantitative RT-PCR reveals an 18% increase in PECAM mRNA in VEGF(164)-treated whole lung cultures as compared with untreated cultures. The restricted temporal and spatial expression of VEGF suggests that matrix-associated VEGF links airway branching with blood vessel formation by stimulating neovascularization at the leading edge of branching airways.
Links	PubMed Online version:<::AID-DVDY1061>3.0.CO;2-M 10.1002/1097-0177(2000)9999:9999<::AID-DVDY1061>3.0.CO;2-M
Keywords	Animals; Antigens, CD31/genetics; Antigens, CD31/metabolism; Base Sequence; Culture Techniques; DNA Primers/genetics; Endothelial Growth Factors/genetics; Endothelial Growth Factors/metabolism; Endothelial Growth Factors/pharmacology; Gene Expression Regulation, Developmental; Immunohistochemistry; Lung/blood supply; Lung/embryology; Lung/metabolism; Lymphokines/genetics; Lymphokines/metabolism; Lymphokines/pharmacology; Mice; Models, Biological; Neovascularization, Physiologic/drug effects; Protein Isoforms/genetics; Protein Isoforms/metabolism; RNA, Messenger/genetics; RNA, Messenger/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Thrombomodulin/metabolism; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:VEGFA	acts_upstream_of_or_within	GO:0060426: lung vasculature development	ECO:0000314: direct assay evidence used in manual assertion		P	occurs_in:(EMAPA:16728)	Seeded From UniProt	complete

References

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