Molecular basis for the control of intractable diseases through manipulation of osteopontin function.

通过操纵骨桥蛋白功能控制难治性疾病的分子基础。

• 批准号: 16209014
• 负责人: UEDE Toshimitsu
• 金额: $ 25.46万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16209014/
• 关键词: Osteopontin; neutralizing antibody; rheumatoid arthritis; integrin; siRNA; 脱接着; 癌転移; RNAアプタマー

It has been shown that the cryptic epitope, S162VVYGLR168, is exposed by the cleavage of human osteopontin (OPN) by thrombin and this epitope is recognized by a 4 and a 9 integrins.1) We found that V164, Y105 and L167 residues are critical for the recognition by both a 9 and a 4 integrins in terms of cell adhesion and migration. While, R168 residue is critical for the recognition by a 9 integrin in cell adhesion and V163 is important for a 4 integrin in cell migration.2) We also found that R168 residue transmits negative signal for Rho mediated-function when SVVYGLR is recognize by a 4 and a 9 integrins in cell migration.3) OPN is also cleaved by MMP-3 and MMP-7 at a position of SVVYG166/L167R. We found that a 4 integrin, but not a 9 integrin is able to recognized MMP-cleaved from of OPN.

已经表明，隐藏表位S162 VVYGLR 168通过凝血酶切割人骨桥蛋白（OPN）而暴露，并且该表位被α 4和α 9整联蛋白识别。1）我们发现V164、Y105和L167残基对于α 9和α 4整联蛋白在细胞粘附和迁移方面的识别是关键的。虽然，R168残基是α 9整合素在细胞粘附中识别的关键，V163是α 4整合素在细胞迁移中识别的关键。2）我们还发现，当SVVYGLR被α 4和α 9整合素识别时，R168残基传递了Rho介导的功能的负信号。3）OPN也在SVVYG 166和α 9整合素的位置被MMP-3和MMP-7切割。L167R我们发现α 4整合素，而不是α 9整合素能够识别MMP切割的OPN。

项目成果

Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases

• DOI: 10.1016/j.immuni.2004.08.012
• 发表时间: 2004-10-01
• 期刊: IMMUNITY
• 影响因子: 32.4
• 作者: Diao, HY;Kon, S;Uede, T
• 通讯作者: Uede, T

Effect of osteopontin alleles on β-grucan induced granuloma formation in the mouse liver.

骨桥蛋白等位基因对β-葡聚糖诱导的小鼠肝脏肉芽肿形成的影响。

• 发表时间: 2004
• 期刊: Am J Pathol. 164
• 作者: Cerrato;F.;et al.;K.Tanaka
• 通讯作者: K.Tanaka

Osteopontin functionally activates dendritic cells and induces their differentiation towards a Th-1 polarizing phenotype.

骨桥蛋白功能性地激活树突状细胞并诱导其向 Th-1 极化表型分化。

• 发表时间: 2005
• 期刊: Blood. 106
• 作者: AC.Renkl

Osteopontin affects the persistence of β-glucan-induced hepatic granuloma formation and tissue injury through two distinct mechanisms

• DOI: 10.1093/intimm/dxh044
• 发表时间: 2004-03-01
• 期刊: INTERNATIONAL IMMUNOLOGY
• 影响因子: 4.4
• 作者: Morimoto, J;Inobe, M;Uede, T
• 通讯作者: Uede, T

Circulating interleukin-18 and osteopontin are useful to evaluate disease activity in patients with tuberculosis

• DOI: 10.1016/j.cyto.2005.01.014
• 发表时间: 2005-05-21
• 期刊: CYTOKINE
• 影响因子: 3.8
• 作者: Inomata, S;Shijubo, N;Uede, T
• 通讯作者: Uede, T