Soluble Flt-1 (soluble VEGFR-1), a potent natural antiangiogenic molecule in mammals, is phylogenetically conserved in avians.
The flt-1 gene encodes for both the full-length receptor Flt-1 (VEGFR-1) and a soluble form designated sFlt-1. sFlt-1 carries the VEGF-binding domain of Flt-1 as well as a 31-amino-acid stretch derived from an intron and tightly binds VEGF, suppressing its angiogenic activity. The flt-1 gene has so far been identified only in mammals and is highly expressed in placenta as well as in vascular endothelial cells. In placenta, sFlt-1 is abundant in the trophoblast layer during pregnancy, suggesting that it is a negative regulator to excess angiogenesis and vascular permeability at the feto-maternal border in mammals. However, we show here for the first time that the flt-1 gene exists and is highly conserved in chickens. Surprisingly, the chicken flt-1 gene also encodes for sFlt-1 in addition to the full-length receptor. Similar to the mammalian sFlt-1, chicken sFlt-1 carries the VEGF-binding domain and a 31-amino-acid carboxyl region derived from an intron, which was significantly homologous to that in mammals. Chicken sFlt-1 is expressed early in embryogenesis. These findings strongly suggest that the natural antiangiogenic molecule sFlt-1 is widely conserved in vertebrates and regulates the angiogenic process.
Yamaguchi
Sachiko
S
Division of Genetics, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo, 108-8639, Japan.
Iwata
Kumi
K
Shibuya
Masabumi
M
D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002645:Chickens / Q000235:genetics* / Q000378:metabolism; D017124:Conserved Sequence; D006801:Humans; D008322:Mammals / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000502:physiology; D017978:Receptors, Growth Factor / Q000235:genetics; D040262:Receptors, Vascular Endothelial Growth Factor; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D040281:Vascular Endothelial Growth Factor Receptor-1
D020533:Angiogenesis Inhibitors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D040262:Receptors, Vascular Endothelial Growth Factor; D040281:Vascular Endothelial Growth Factor Receptor-1