Expression of adhesion molecules and growth factors in vascular endothelial cell

血管内皮细胞粘附分子和生长因子的表达

• 批准号: 08670788
• 负责人: KUME Noriaki
• 金额: $ 1.47万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670788/
• 关键词: Atherosclerosis; endothelial cells; lysophosphatidylcholine; MAP kinases; tyrosine phosphorylation; PECAM-1; チロシニリン酸化; PECANM-1; 接着分子; atherosclerosis; endothelial cells; lysophosphatidylcholine; tyrosine phosphorylation

Endothelial-leukocyte adhesion molecules such as VCAM-1 and ICAM-1, have been implicated in recruitment of circulating monocytes and T-lymphocytes to atherosclerotic lesions. In addition, smooth muscle growth factors, including PDGF A and B chains and HB-EGF, appear to play crucial role in migration and proliferation of medical smooth muscle cells into atherosclerotic intima. Lysophosphatidylcholine (Ox-LDL), can transcriptionally induce expression of VCAM-1, ICAM-1, PFGF, and HB-EGF in cultured vascular endothelial cells; therefore, we sought to define transcriptional and sibnal transduction mechanisms involved in lyso-PC-induced expression. We have found that elevated levels of intracelluar cyclic AMP inhibited lyso-PC-induced expression of PDGF and ICAM-1. Furthermore, lyso-PC-induced expression of PDGF was dependent upon protein tyrosine phosphorylation. We, therefore, explored the protein that can rapidly phosphorylated in the tyrosine residue. We revealed that a protein with a molecular mass of 130kDa, which was designated p130, was rapidly and transiently tyrosine phosphorylated by lyso-PC. By use of immunoblotting and immunoprecipitation, we have identified p130 as PECAM-1 which was expressed on the intercellular junction of cultured endothelial cells. Our study also have demonstrated that MAP kinases, such as ERK and JNK, were activated by lyso-PC, which appeared to depend upon protein tyrosine phosphorylation.

内皮细胞-白细胞粘附分子如VCAM-1和ICAM-1参与了循环单核细胞和T淋巴细胞向动脉粥样硬化病变的募集。此外，平滑肌生长因子，包括PDGF A和B链和HB-EGF，似乎在医学平滑肌细胞向动脉粥样硬化内膜的迁移和增殖中起关键作用。溶血磷脂酰胆碱（Ox-LDL），可以转录诱导VCAM-1，ICAM-1，PFGF，HB-EGF在培养的血管内皮细胞的表达，因此，我们试图确定参与溶血PC诱导表达的转录和sibnal转导机制。我们已经发现，细胞内cAMP水平升高抑制lyso-PC诱导的PDGF和ICAM-1的表达。此外，lyso-PC诱导的PDGF表达依赖于蛋白酪氨酸磷酸化。因此，我们探索了能够快速磷酸化酪氨酸残基的蛋白质。我们发现，一个分子量为130 kDa的蛋白质，命名为p130，快速和瞬时酪氨酸磷酸化的溶血PC。通过免疫印迹和免疫沉淀，我们已经确定p130为PECAM-1，它表达于培养的内皮细胞的细胞间连接。我们的研究还表明，MAP激酶（例如ERK和JNK）被lyso-PC激活，这似乎取决于蛋白质酪氨酸磷酸化。

项目成果

Hideaki Moriwaki, Noriaki Kume, Tatsuya Sawamura, Takuma Aoyama, Hajime Hoshikawa, Hiroshi Ochi, Eiichiro Nishi, Tomoh Masaki, Toru Kita: "Ligand specificity of lOX-1, a novel endothelial receptor for oxidized low density lipoprotein."Arterioscler.Thromb.

Hideaki Moriwaki、Noriaki Kume、Tatsuya Sawamura、Takuma Aoyama、Hajime Hoshikawa、Hiroshi Ochi、Eiichiro Nishi、Tomoh Masaki、Toru Kita：“lOX-1 的配体特异性，氧化低密度脂蛋白的一种新型内皮受体。”动脉硬化器。血栓。

Hideaki Moriwaki, Noriaki Kume, Hiroharu Kataoka, Takatoshi Murase, Eiichiro Nishi, Tatsuya Sawamura, Tomoh Masaki, Toru Kita: "Expression of lectin-like oxidized low density lipoprotein receptor-1 in human and murine macrophages-upregulated expression by

Hideaki Moriwaki、Noriaki Kume、Hiroharu Kataoka、Takatoshi Murase、Eiichiro Nishi、Tatsuya Sawamura、Tomoh Masaki、Toru Kita：“人类和小鼠巨噬细胞中凝集素样氧化低密度脂蛋白受体 1 的表达上调

Takatoshi Murase,Noriaki Kume,et al: "Fluid shear stress transcriptionally induces lectin-like oxidized LDL receptor-1 in vascular endothelial cells"Circulation Research. vol.83. 328-333 (1998)

Takatoshi Murase、Noriaki Kume 等人：“流体剪切应力转录诱导血管内皮细胞中凝集素样氧化 LDL 受体 1”循环研究。

Hideaki Moriwaki,Noriaki Kume,et al: "Ligand specificity of LOX-1,a novel endothelial receptor for oxidized low density lipoprotein"Arterioscler.Thromb.Vasc.Biol. vol.18. 1541-1547 (1998)

Hideaki Moriwaki、Noriaki Kume 等人：“LOX-1 的配体特异性，氧化低密度脂蛋白的新型内皮受体”Arterioscler.Thromb.Vasc.Biol。

Eiichiro Nishi, Noriaki Kume, Hiroshi Ochi, Hideaki Moriwaki, Yoshio Wakutsuki, Shigeki Higashiyma, Shigeki Higashiyama, Naoyuki Taniguchi, Toru Kita: "Lysophosphatidycholine increases expression of heparin-binding epidermal growth factor-like growth fact

Eiichiro Nishi、Noriaki Kume、Hiroshi Ochi、Hideaki Moriwaki、Yoshio Wakutsuki、Shigeki Higashiyma、Shigeki Higashiyama、Naoyuki Taniguchi、Toru Kita：“溶血磷脂胆碱增加肝素结合表皮生长因子样生长因子的表达