Development of effective inhibitors against carbohydrate recognition adhesion molecules involved in invasion of inflammatory cells and/or cancer cells.

开发针对参与炎症细胞和/或癌细胞侵袭的碳水化合物识别粘附分子的有效抑制剂。

• 批准号: 08557025
• 负责人: MIYASAKA Masayuki
• 金额: $ 7.81万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 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/grant/KAKENHI-PROJECT-08557025/
• 关键词: selectin; CD44; proteoglycan; versican; anti-inflammatory agent; leukocyte; acute inflammation; adhesion molecules; 抗炎症剤

1. We have for the first time succeeded in identifying versican as a ligand for a leukocyte adhesion molecule, L-selectin. Versican is a large chondrotin sulfate proteoglycan produced by fibroblasts. Unlike other ligands for L-selectin, versican is not modified with sialyl Lewis X type carbohydrates, but has chondroitin sulfate side chains which interacts with the lectin domain of L-selectin. Versican is localized in epithelial cells of distal tubules of the kidney under physiological conditions, but is rapidly released from there under pathological conditions. The shed versican is then recognized by leukocyte L-selectin, which may promote tissue injury.2. Versican can bind to not only L-selectin but also other inflammatory adhesion molecules, such as P-selectin and CD44. In addition, it can capture a certain type of chemokines on its chondrotin sulfate side chains, which may result in augmenting inflammatory responses. It was revealed that functional inhibition of L-selectin leads to inhibition of interstitial nephritis induced by ureteral obstruction.3. We have found a substance that can inhibit fucosylation and sialylation of cell surface proteins.

1。我们首次成功地将versican鉴定为白细胞粘附分子L-选择素的配体。 Versican是由成纤维细胞产生的大型软骨硫酸盐蛋白聚糖。与其他用于L-选择蛋白的配体不同，Versican不会用siAllyl Lewis X型碳水化合物修饰，而是具有与L-链蛋白的lectin结构域相互作用的硫酸软骨侧链。 Versican位于生理条件下肾脏远端小管的上皮细胞中，但在病理条件下迅速从那里释放。然后，白细胞L-选择蛋白可以识别棚屋，这可能会促进组织损伤2。 Versican不仅可以与L-选择素，还可以与其他炎症粘附分子（例如P-选择素和CD44）结合。此外，它可以捕获硫酸软骨软骨侧链上的某种类型的趋化因子，这可能导致炎症反应增加。据表明，功能抑制L-选择素会导致输尿管阻塞诱导的间质肾炎的抑制。3。我们发现了一种可以抑制细胞表面蛋白的岩藻糖基化和苷化的物质。

项目成果

Kawashima,H.et al.: "Characterization of a 180 kDa molecule apparently reactive with recombinant L-selectin." Glycoconjugate J.14. 321-330 (1997)

Kawashima, H.et al.：“180 kDa 分子的表征，明显与重组 L-选择素发生反应。”

Kawashima, H.et al.: "Characterization of a 180kDa molecule apparently reactive with recombinant L-selectin." Glycoconjugate J.14. 321-330 (1997)

Kawashima, H.et al.：“180kDa 分子的表征，明显与重组 L-选择素发生反应。”

Kurose,I.: "Microvascular dysfunction induced by nonsteroidal anti-inflammatory drugs:role of leukocytes." Am.J.Physiol.270. G363-G369 (1996)

Kurose,I.：“非甾体类抗炎药引起的微血管功能障碍：白细胞的作用。​​”

Miyasaka,M.et al.: "Involvement of selectins in atherogenesis:A primary or secondary event?" Ann.N.Y.Acad.Sci.811. 25-35 (1997)

Miyasaka,M.et al.：“选择素参与动脉粥样硬化形成：原发性还是继发性事件？”

Kawashima, H.et al.: "Characterization of a 180 kDa molecule apparently reactive with recombinant L-selectin." Glycoconjugate J.14. 321-330 (1997)

Kawashima, H.et al.：“180 kDa 分子的表征，明显与重组 L-选择素发生反应。”