血管内皮細胞のタイト結合蛋白7H6とがん細胞の血管外脱出の抑制

血管内皮细胞紧密连接蛋白7H6及其抑制癌细胞外渗

• 批准号: 08265253
• 负责人: 澤田 典均
• 金额: $ 1.73万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-08265253/
• 关键词: タイト結合; ZO-1; 7H6(barmotin); 細胞電気抵抗; SMC蛋白

1.目的血管内皮細胞間にはタイト結合が存在し、イオンや蛋白のみならず炎症細胞や癌細胞のintra-およびextra-vasationに関与していると考えられている。したがって、タイト結合の機能(バリア機能)を調節することにより癌細胞の血管への出入りを制御できる可能性がある。我々が発見したタイト結合蛋白のひとつ、7H6蛋白(barmotin)の発現はバリア機能と相関するため、barmotinのcDNA発現クローニング、シークエンスを行い、barmotinの機能を明らかにすると共に、タイト結合の機能調節機構を明かにする。2.方法と結果1)株化した肺毛細血管内皮細胞(RLE)をtranswellに単層培養し、その電気抵抗(transendothelial electrical resistance:TER)を測定することにより、タイト結合のバリア機能を評価したところ、db-cAMPとretinoic acidは有意にTERを上昇させるとともに7H6の細胞辺縁への発現を誘導した。この時RLEへの癌細胞のもぐりこみは、対照に比べ約60%抑制された。同様の結果は、腹腔中皮細胞を用いた研究でも得られた。2)Barmotinは、1184aaからなる蛋白で、既知の蛋白には高いホモロジーを示すものはなかった。構造を調べると、N末とC末にそれぞれWalker's A siteとWalker's B siteと呼ばれるATPaseに特徴的なドメイン構造が離れて存在し、両ドメインの間にはふたつのcoiled coilドメインを有していた。このような構造は最近発見された分子モーターSMC familyに特徴的で、barmotinはSMC1 subfamilyに属することが明らかとなった。

1. Objective To investigate the relationship between vascular endothelial cells and extra-vasation. It is possible to regulate the function of combination of cancer cells and vascular access control. We found that the protein binding mechanism of barmotin, 7H6 protein (barmotin) and its expression function were related, the cDNA expression of barmotin was related, the function of barmotin was related, and the regulatory mechanism of barmotin binding function was related. 2. Methods 1) Transendothelial electrical resistance (TER) of cultured pulmonary capillary endothelial cells (RLE) was measured in single layer culture, and the expression of TER was induced by db-cAMP retinoic acid. This time RLE cancer cells were inhibited by 60% of the control group. The same results were obtained from the study of mesothelioma cells in abdominal cavity. 2)Barmotin, 1184aa, protein, known protein The structure of the enzyme is composed of Walker's A site and Walker's B site. The structure of the enzyme is composed of two parts: one part is composed of Walker's A site and Walker's B site. The other part is composed of Walker's A site and Walker's B site. The other part is composed of Walker's A site and Walker's B site. The structure of the enzyme is composed of two parts: Walker's A site and Walker's B site. The structure of the enzyme is composed of two parts: Walker's A site and Walker's B site. The structure of the enzyme is composed of two parts: Walker's A site and Walker's B site. The structure of the enzyme is composed of two parts: Walker's A site and Walker's B site. The structure of the SMC family was recently discovered, and the SMC family was characterized by barmotin.

项目成果

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