| Research Abstract |
The purpose of this study was to investigate endothelial gene which were responsive to shear stress generated by blood flow and to find genes encoding new bio-active substances. First, in order to evaluate whole number of shear stress-responsive genes in endothelial cells, differential display of mRNAs was performed. The results showed that 33 of 15O7mRNAs detected were up-regulated by a shear stress of 15 dynes/cm^2 for 6 h, while 27 were down-regulated, indicating that around 4% of the whole endothelial genes are shear-sensitive. Second, 16 genes were cloned from these 60 shear-sensitive genes and sequenced. Homology search revealed 6 known genes encoding laminin B1 chain, H^+-ATP synthase coupling factor 6, lysyl oxidase, myosin light chain kinase, NADH dehydrogenase, and interleukin-8 receptor and 10 unknown genes. Lastly, we constructed a cDNA library from human umbilical vein endothelial cells which had been exposed to a shear stress of 15 dynes/cm^2 for 8 h, and looked for new G-protein coupled receptors. As a result we obtained a new one which we named PEG-1 (Flow-induced Endothelial G-protein-coupled receptor. The receptor consists of 375 amino acids and has a homology to angiotensin receptors or chemokine receptors.
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