Elucidation of the relation between multi-ligand receptor, FEEL and diseases

阐明多配体受体、FEEL与疾病之间的关系

• 批准号: 16390027
• 负责人: ADACHI Hideki
• 金额: $ 4.29万
• 依托单位: RIKEN
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-16390027/
• 关键词: FEEL; arteriosclerosis; diabetes; スカベンジャー受容体; 血管内皮細胞; ノックアウトマウス

Multiligand receptors (scavenger receptors) are defined as its ability to recognize several structurally and functionally dissimilar molecule such as modified lipoproteins, advanced glycation end-products (AGE) and apoptotic cells. It is suggested that they were implicated in various diseases such as arteriosclerosis and diabetes. Employing expression cloning, we have cloned a multiligand receptor termed FEEL-1 (fasciclin, EGF-like, laminin-type EGF-like and link domain-containing scavenger receptor-1) expressed in human endothelial cells and subsequently cloned FEEL-2 by data base search. The receptors had binding activities to modified lipoproteins, cells of both Gram-positive, Gram-negative bacteria and AGE. Soluble form of human FEEL-1 was expressed using adenoviral vector, and the binding activities of soluble form of FEEL-1 to acetyl-LDL or AGE were determined. Expression of miRNA (micro RNA) against FEEL employing fiber mutant adenoviral vector in murine liver sinusoidal endothelial cells suggested that both FEEL-1 and FEEL-2 contribute to the hepatic reticuloendothelial system in clearance of waste materials from blood flow. Knockout mice of FEEL-1 or FEEL-2 were generated by gene targeting. Determination of the physiological function of FEEL will provide a new insight into the pathological function of this multiligand receptor.

多配体受体（scavenger receptor）被定义为识别多种结构和功能不同的分子的能力，如修饰的脂蛋白、晚期糖基化终产物（AGE）和凋亡细胞。这表明，他们牵连在各种疾病，如动脉硬化和糖尿病。采用表达克隆，我们已经克隆了一个多配体受体FEEL-1（fasciclin，EGF样，层粘连蛋白型EGF样和链接域含有清道夫受体-1）在人内皮细胞中表达，随后克隆FEEL-2的数据库搜索。这些受体对修饰的脂蛋白、革兰氏阳性菌、革兰氏阴性菌细胞和AGE均有结合活性。使用腺病毒载体表达可溶形式的人FEEL-1，并测定可溶形式的FEEL-1与乙酰-LDL或AGE的结合活性。使用纤维突变腺病毒载体在鼠肝窦内皮细胞中表达针对FEEL的miRNA（microRNA）表明FEEL-1和FEEL-2都有助于肝网状内皮系统从血流中清除废物。通过基因打靶产生FEEL-1或FEEL-2的敲除小鼠。FEEL的生理功能的测定将为这种多配体受体的病理功能提供新的见解。