The biological effects of vascular endothelial growth factor A (VEGF-A) are mediated by fetal liver kinase-1 (Flk-1) and fms-like tyrosine kinase-1 (Flt-1). In lung tissue, VEGF-A is diffusely expressed throughout the embryonic stages, whereas the development of vascular endothelial cells is not uniform. Noting the signaling properties of the two receptors, we hypothesized that Flk-1 and Flt-1 regulate the embryonic development of lung vasculature. We herein show the spatiotemporal expression and experimental inhibition of Flk-1 and Flt-1 of embryonic mouse lung tissue. When Flk-1 was predominantly expressed (embryonic day [E] 9.5-E13.5), then vascular endothelial cells actively proliferated. When Flt-1 was enhanced (E14.5-E16.5), these cells less actively proliferated, thereby constituting organized networks. The treatment of cultured lung buds (E11.5) with antisense oligonucleotides complementary to Flk-1 inhibited branching of capillaries and proliferation of endothelial cells. In contrast, the inhibition of Flt-1 promoted the branching of capillaries and enhanced proliferation of endothelial cells. Of interest, inhibition of Flt-1 promoted Flk-1 expression. These results suggest that the two VEGF-A receptors regulate pulmonary vascular development by modulating the VEGF-A signaling.
Pubmed ID: 17654674 RIS Download
Mesh terms: Animals | Cell Proliferation | Endothelium, Vascular | Ephrin-B2 | Female | Gene Expression Regulation, Developmental | Lung | Mice | Mice, Inbred ICR | Morphogenesis | Neovascularization, Physiologic | Oligodeoxyribonucleotides, Antisense | Pregnancy | RNA, Messenger | Signal Transduction | Vascular Endothelial Growth Factor A | Vascular Endothelial Growth Factor Receptor-1 | Vascular Endothelial Growth Factor Receptor-2
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