血管障害性疾患に対する新規なリスク分子・標的治療分子の探索研究

血管疾病新型风险分子和靶向治疗分子的探索性研究

• 批准号: 17790207
• 负责人: 岡本 貴行
• 金额: $ 2.18万
• 依托单位: Mie University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17790207/
• 关键词: ファージディスプレイ法; 血管内皮細胞; 血液凝固; 炎症性血管病変; ギャップ結合; 血液凝固反応; 炎症反応; 生理活性ペプチド

・研究の背景血管障害性疾患の多くは、血液凝固反応、炎症反応が慢性的に活性化した炎症性血管病変を基盤とする。そのため、新しい血管障害性疾患の診断・治療法の開発には、血管内皮細胞に対して抗血栓性、抗炎症性作用を示す生理活性ペプチドの探索とその作用機序の解明が有効であると考えられる。これまで私は、ファージディスプレイ法を用いて血管内皮細胞に結合するペプチドの探索に成功している。本研究は、このペプチドが血管内皮細胞に及ぼす作用およびペプチドが結合する細胞側受容体分子の解明を行う。・研究目的血管内皮細胞に結合するペプチドの細胞側受容体分子の同定とこの受容体の生理機能を解析し、血液凝固反応、炎症反応に与える影響を解析する。さらに、同定したペプチドや受容体を標的とした血管障害性疾患の診断法・治療法・予防法の開発へ応用することを目的とする。これまでの研究成果に基づき、最終報告を提出する。・研究成果これまでに同定したペプチドのアミノ酸配列を解析した結果、このペプチドはギャップ結合を構成するコネキシン32(connexin32:Cx32)と相同性を有していた。ペプチドが血管内皮細胞に発現するCx32と結合していると考え、血管内皮細胞にCx32が発現すること、ペプチドとCx32が結合すること、血管内皮細胞間の相互作用にCx32が関わることを明らかにした。しかし、血管内皮細胞でのCx32の機能は全く知られておらず、私は、炎症性サイトカイン刺激によりCx32の発現量が減少すること、Cx32強制発現細胞では炎症性サイトカインの分泌が低下することを示し、Cx32によるギャップ結合が血管内皮細胞の機能維持に重要な役割を持つことを示した。

Background: multiple vascular disorders, blood coagulation, inflammatory reaction, chronic activation, inflammatory vascular disease, inflammatory disease. The antithrombotic and anti-inflammatory effects of antithrombotic and anti-inflammatory effects of vascular endothelial cells were detected in order to explore the mechanism of action and to explain the mechanism of action. We used the combination of vascular endothelial cells and vascular endothelial cells to explore the success of the method. In this study, the vascular endothelial cells and the vascular endothelial cells were combined with the capacitive molecules of the vascular endothelial cells. Objective the purpose of this study was to analyze the physiological function, blood coagulation reaction, inflammatory reaction and immune response of vascular endothelial cells combined with the molecules of cell capacitors. The treatment of vascular disorders, the treatment of vascular disorders, the prevention and treatment of vascular disorders, the prevention and treatment of vascular diseases, the prevention and treatment of vascular disorders, the prevention and treatment of vascular disorders, the prevention and treatment of vascular disorders, the prevention and treatment of vascular disorders, the prevention and treatment of vascular disorders, the prevention and treatment of vascular disorders, the prevention and treatment of vascular disorders, the prevention and treatment of vascular disorders, the prevention and treatment of vascular disorders, the prevention and treatment of vascular disorders, the prevention and treatment of vascular disorders, the prevention and treatment of vascular disorders, the prevention and treatment of vascular diseases, the prevention and treatment of vascular diseases, the prevention and treatment of vascular diseases. The research results are based on the basis of the research results and the most recent reports are presented. The results of the study are consistent with the results of the analysis of the results of the research. The results of the study were analyzed by the combination of the results of the study and the results of the analysis of the results of the research. The results of the study showed that the results of the study were consistent with the results of the analysis of the results of the study. The results of the study were analyzed in terms of the results of the analysis of the results of the study. The results of the study were analyzed in the same way as in the analysis of the results of the study. The results of the study were analyzed by the combination of the results of the analysis and the combination of the results of the study. (connexin32:Cx32) The results of Cx32 assay, intercellular interaction and Cx32 assay showed that there was no significant difference between the two groups. Anti-inflammatory, vascular endothelial cell-specific Cx32 can be used to know that it is important to maintain the vital importance of Cx32 in combination with vascular endothelial cell cytoskeleton. The stimulation of inflammatory cell-specific immune response (Cx32), low secretion of inflammatory cell-secreting cell (low-secretion), and vascular endothelial cell cycle (Cx32-Elisa) can maintain the vital function of the vascular endothelial cell.

项目成果

Annual Review 血液

年度审查血液

• 发表时间: 2015
• 作者: 門平靖子;松浦絵里香;林朋恵;森下英理子;朝倉英策;Asakura H;朝倉英策;朝倉英策;朝倉英策;朝倉英策;朝倉英策;朝倉英策;朝倉英策;朝倉英策;朝倉英策;朝倉英策;朝倉英策;朝倉英策;朝倉英策（分担）;朝倉英策（単著）;朝倉英策（分担）;朝倉英策（分担）;朝倉英策（分担）;朝倉英策（分担）;朝倉英策（単著）
• 通讯作者: 朝倉英策（単著）

Optimization of anti-tumor necrosis factor-alpha single chain Fv displayed on phages for creation of functional antibodies.

优化噬菌体上展示的抗肿瘤坏死因子-α 单链 Fv，用于创建功能性抗体。

• 发表时间: 2006
• 期刊: Pharmazie. 61・10
• 作者: Sato Y;Nakanuma Y et al.;Sato Y.et al.;Sato Y.et al.;Kamada H et al.;Fujii K et al.;Kawamura M et al.;Mukai Y et al.
• 通讯作者: Mukai Y et al.

Differential regulation of protein S expression in hepatocytes and sinusoidal endothelial cells in rats with cirrhosis

• DOI: 10.1111/j.1538-7836.2006.02227.x
• 发表时间: 2006-12-01
• 期刊: JOURNAL OF THROMBOSIS AND HAEMOSTASIS
• 影响因子: 10.4
• 作者: Fujii, K.;Kishiwada, M.;Suzuki, K.
• 通讯作者: Suzuki, K.

Creation of novel cell-penetrating peptides for intracellular drug delivery using systematic phage display technology originated from tat transduction domain

• DOI: 10.1248/bpb.30.218
• 发表时间: 2007-02-01
• 期刊: BIOLOGICAL & PHARMACEUTICAL BULLETIN
• 影响因子: 2
• 作者: Kamada, Haruhiko;Okamota, Takayuki;Tsunoda, Shin-ichi
• 通讯作者: Tsunoda, Shin-ichi

A novel method for construction of gene fragment library to searching epitopes

一种构建基因片段库寻找表位的新方法

• 发表时间: 2006
• 期刊: Biochem. Biophys. Res. Commun. 346
• 作者: Nishikawa M;Hashida M;Kawamura et al.
• 通讯作者: Kawamura et al.