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Publication : Regulation of embryonic lung vascular development by vascular endothelial growth factor receptors, Flk-1 and Flt-1.

First Author  Yamamoto Y Year  2007
Journal  Anat Rec (Hoboken) Volume  290
Issue  8 Pages  958-73
PubMed ID  17654674 Mgi Jnum  J:126692
Mgi Id  MGI:3761881 Doi  10.1002/ar.20564
Citation  Yamamoto Y, et al. (2007) Regulation of embryonic lung vascular development by vascular endothelial growth factor receptors, Flk-1 and Flt-1. Anat Rec (Hoboken) 290(8):958-73
abstractText  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.
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