|Budget Amount *help
¥3,500,000 (Direct Cost : ¥3,500,000)
Fiscal Year 2002 : ¥1,200,000 (Direct Cost : ¥1,200,000)
Fiscal Year 2001 : ¥2,300,000 (Direct Cost : ¥2,300,000)
Ross's "the response-to-injury hypothesis of atherosclerosis" in the development of atherosclerosis is commonly accepted. Scavenger receptors mediate the endocytosis of chemically modified lipoproteins, such as acetylated low-density lipoprotein (Ac-LDL) and oxidized LDL (Ox-LDL), and have been implicated in the most important role for the hypothesis. The cDNAs of scavenger receptor gene family have been cloned and. its structures were deduced. LOX-1, a major receptor of oxidized LDL, SREC (scavenger receptor expressed by endothelial cell) cloned by expression cloning from human umbilical vein endothelial cells and CD36 are expressed in endothelial cells. These scavenger receptors recognize several negatively charged molecule such as modified lipoproteins and apoptic cells, and suggested for some roles in various diseases.
We cloned a novel scavenger receptor termed FEEL-1 expressed in endothelial cells that was structurally unrelated to other scavenger receptors by expression cloning. The cloned receptor contained fasciclin (Fas-1), EGF-like, laminin-type EGF-like and link domains. Based on the domain structures, we temporary termed it FEEL-1 (fasciclin, EGF-like, laminin-type EGF-like and link domain-containing scavenger receptor-1). Database search suggested the presence of a paralogous gene of FEEL-1, the full-length cDNA of this gene was also cloned and its nucleotide sequence was determined. The deduced amino acid sequence of the clone indicated that its domain organization is similar to FEEL-1 and we termed this clone FEEL-2. The receptor had binding activity to cells of both Gram-positive and Gram-negative bacteria and advaned glycation end product. Moreover, in vitro tube formation assay suggested that the receptor might play a role in angiogenesis. These results suggest that FEELs play important roles in the defense mechanisms against bacterial infection, atherosclerosis and diabet.