Investigation of mechanism of pulmonary fibrosis focusing on post-translational modification of osteopontin and its receptor change

以骨桥蛋白翻译后修饰及其受体变化为研究对象的肺纤维化机制

• 批准号: 18590853
• 负责人: YOKOSAKI Yasuyuki
• 金额: $ 2.57万
• 依托单位: Hiroshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590853/
• 关键词: Pulmonary Fibrosis; Osteopontin; Integrin; Neutrophil; Chemoattractant; トランスグルタミナーゼ; 重合

We investigated mechanism of pulmonary fibrosis focusing on post-translational modifications of osteopontin and associating receptor change.1) Osteopontin was polymerized by transglutaminase 2.2) Cell adhesion, spreading, and migration were enhanced when cells were plated on polymeric osteopontin than on monomeric osteopontin.3) Focal contact formation in cells plated on polymeric osteopontin was dramatic, which suggests the cell behaviors described above were mediated by integrin receptors.4) Polymeric osteopontin induces neutrophil migration in vitro, which was analyzed by horizontal migration analysis apparatus, Taxiscan.5) Polymeric osteopontin recruited neutrophils into mouse peritoneal space.These results suggest that polymerization of osteopontin is involved in lung injury induced by neutrophils, the first step of pulmonary fibrosis. Although we could not describe in this report, we are on a process of generating osteopontin mutant mice to confirm the effects of polymerization of osteopontin on pulmonary fibrosis.

我们研究了肺纤维化的机制，重点是骨桥蛋白的翻译后修饰和相关受体的变化。1）骨桥蛋白被转氨酶聚合。2）细胞在聚合骨桥蛋白上的粘附、铺展和迁移比在单体骨桥蛋白上的增强。3）在聚合骨桥蛋白上的细胞中的局部接触形成是显著的，这表明上述细胞行为是由整联蛋白受体介导的。4）多聚骨桥蛋白在体外诱导中性粒细胞迁移，这通过水平迁移分析装置分析，Taxiscan.5）多聚骨桥蛋白募集中性粒细胞进入小鼠腹腔，提示骨桥蛋白的多聚化参与了肺组织的炎症反应，中性粒细胞引起的损伤是肺纤维化的第一步。虽然我们不能在这份报告中描述，我们正在产生骨桥蛋白突变小鼠的过程中，以确认骨桥蛋白聚合对肺纤维化的影响。

项目成果

Enhanced biological activity of polymeric osteopontin

• DOI: 10.1016/j.febslet.2007.05.018
• 发表时间: 2007-06-12
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Higashikawa, Fumiko;Eboshida, Akira;Yokosaki, Yasuyuki
• 通讯作者: Yokosaki, Yasuyuki

Polymeric osteopontin is a potent chemoattractant for neutrophils mediated by Integrins

聚合骨桥蛋白是整合素介导的中性粒细胞的有效化学引诱剂

• 发表时间: 2007
• 作者: Yokosaki;Y.;et. al.
• 通讯作者: et. al.

トランスグルタミナーゼ2はオステオポンチンを重合し好中球の遊走を惹起する

转谷氨酰胺酶 2 聚合骨桥蛋白并诱导中性粒细胞迁移

• 发表时间: 2007
• 作者: Imaizumi;K;et. al.;横崎恭之
• 通讯作者: 横崎恭之

Gene-environment association of an ITGB2 sequence variant with obesity in ethnic Japanese

• DOI: 10.1038/oby.2008.68
• 发表时间: 2008-06-01
• 期刊: OBESITY
• 影响因子: 6.9
• 作者: Awaya, Tomokazu;Yokosaki, Yasuyuki;Eboshida, Akira
• 通讯作者: Eboshida, Akira

Polymeric Osteopontin is a Potent Chemoattractant for Neutrophils Mediated by Integrins.

聚合骨桥蛋白是由整合素介导的中性粒细胞的有效化学引诱剂。

• 发表时间: 2007
• 作者: Yokosaki Y.;et. al.
• 通讯作者: et. al.