| RRC ID |
28681
|
| 著者 |
Watanabe K, Hasegawa Y, Yamashita H, Shimizu K, Ding Y, Abe M, Ohta H, Imagawa K, Hojo K, Maki H, Sonoda H, Sato Y.
|
| タイトル |
Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis.
|
| ジャーナル |
J Clin Invest
|
| Abstract |
Negative feedback is a crucial physiological regulatory mechanism, but no such regulator of angiogenesis has been established. Here we report a novel angiogenesis inhibitor that is induced in endothelial cells (ECs) by angiogenic factors and inhibits angiogenesis in an autocrine manner. We have performed cDNA microarray analysis to survey VEGF-inducible genes in human ECs. We characterized one such gene, KIAA1036, whose function had been uncharacterized. The recombinant protein inhibited migration, proliferation, and network formation by ECs as well as angiogenesis in vivo. This inhibitory effect was selective to ECs, as the protein did not affect the migration of smooth muscle cells or fibroblasts. Specific elimination of the expression of KIAA1036 in ECs restored their responsiveness to a higher concentration of VEGF. The expression of KIAA1036 was selective to ECs, and hypoxia or TNF-alpha abrogated its inducible expression. As this molecule is preferentially expressed in ECs, we designated it "vasohibin." Transfection of Lewis lung carcinoma cells with the vasohibin gene did not affect the proliferation of cancer cells in vitro, but did inhibit tumor growth and tumor angiogenesis in vivo. We propose vasohibin to be an endothelium-derived negative feedback regulator of angiogenesis.
|
| 巻・号 |
114(7)
|
| ページ |
898-907
|
| 公開日 |
2004-10-1
|
| DOI |
10.1172/JCI21152
|
| PMID |
15467828
|
| PMC |
PMC518662
|
| MeSH |
Amino Acid Sequence
Angiogenesis Inhibitors / genetics
Angiogenesis Inhibitors / metabolism*
Animals
Autocrine Communication
Cell Cycle Proteins
Cell Line, Tumor
Cell Movement / physiology
Endothelial Cells / cytology
Endothelial Cells / metabolism*
Endothelium, Vascular / cytology
Endothelium, Vascular / metabolism*
Feedback, Physiological*
Humans
Mice
Molecular Sequence Data
Neovascularization, Pathologic
Neovascularization, Physiologic*
Oligonucleotide Array Sequence Analysis
Proteins / genetics
Proteins / metabolism*
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Sequence Alignment
Tissue Distribution
Vascular Endothelial Growth Factors / metabolism
|
| IF |
11.864
|
| 引用数 |
222
|
|
WOS 分野
|
MEDICINE, RESEARCH & EXPERIMENTAL
|
| リソース情報 |
| 遺伝子材料 |
pcDNA3.1-mycHis-hVASH (RDB08518) |
