• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

基质金属蛋白酶-3/7切割的骨桥蛋白C末端片段中的一种新型隐蔽结合基序LRSKSRSFQVSDEQY作为α9β1整合素的新型配体参与抗II型胶原抗体诱导的关节炎。

A novel cryptic binding motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved osteopontin as a novel ligand for α9β1 integrin is involved in the anti-type II collagen antibody-induced arthritis.

作者信息

Kon Shigeyuki, Nakayama Yosuke, Matsumoto Naoki, Ito Koyu, Kanayama Masashi, Kimura Chiemi, Kouro Hitomi, Ashitomi Dai, Matsuda Tadashi, Uede Toshimitsu

机构信息

Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.

Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.

出版信息

PLoS One. 2014 Dec 29;9(12):e116210. doi: 10.1371/journal.pone.0116210. eCollection 2014.

DOI:10.1371/journal.pone.0116210
PMID:25545242
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4278882/
Abstract

Osteopontin (OPN) is a multifunctional protein that has been linked to various intractable inflammatory diseases. One way by which OPN induces inflammation is the production of various functional fragments by enzyme cleavage. It has been well appreciated that OPN is cleaved by thrombin, and/or matrix metalloproteinase-3 and -7 (MMP-3/7). Although the function of thrombin-cleaved OPN is well characterized, little is known about the function of MMP-3/7-cleaved OPN. In this study, we found a novel motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved mouse OPN binds to α9β1 integrin. Importantly, this novel motif is involved in the development of anti-type II collagen antibody-induced arthritis (CAIA). This study provides the first in vitro and in vivo evidence that OPN cleavage by MMP-3/7 is an important regulatory mechanism for CAIA.

摘要

骨桥蛋白（OPN）是一种多功能蛋白质，与多种难治性炎症性疾病有关。OPN诱导炎症的一种方式是通过酶切产生各种功能片段。人们已经充分认识到，OPN可被凝血酶和/或基质金属蛋白酶-3和-7（MMP-3/7）切割。虽然凝血酶切割的OPN的功能已得到充分表征，但关于MMP-3/7切割的OPN的功能却知之甚少。在本研究中，我们在MMP-3/7切割的小鼠OPN的C末端片段中发现了一个新的基序LRSKSRSFQVSDEQY，它与α9β1整合素结合。重要的是，这个新基序参与了抗II型胶原抗体诱导的关节炎（CAIA）的发展。本研究提供了首个体外和体内证据，表明MMP-3/7切割OPN是CAIA的重要调节机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9572/4278882/823978601ecd/pone.0116210.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9572/4278882/4ebc9d0a29cc/pone.0116210.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9572/4278882/de8192224a94/pone.0116210.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9572/4278882/8fd808c78b69/pone.0116210.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9572/4278882/264162c8dd5f/pone.0116210.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9572/4278882/823978601ecd/pone.0116210.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9572/4278882/4ebc9d0a29cc/pone.0116210.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9572/4278882/de8192224a94/pone.0116210.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9572/4278882/8fd808c78b69/pone.0116210.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9572/4278882/264162c8dd5f/pone.0116210.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9572/4278882/823978601ecd/pone.0116210.g005.jpg

相似文献

1
A novel cryptic binding motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved osteopontin as a novel ligand for α9β1 integrin is involved in the anti-type II collagen antibody-induced arthritis.基质金属蛋白酶-3/7切割的骨桥蛋白C末端片段中的一种新型隐蔽结合基序LRSKSRSFQVSDEQY作为α9β1整合素的新型配体参与抗II型胶原抗体诱导的关节炎。
PLoS One. 2014 Dec 29;9(12):e116210. doi: 10.1371/journal.pone.0116210. eCollection 2014.
2
Osteopontin, a novel substrate for matrix metalloproteinase-3 (stromelysin-1) and matrix metalloproteinase-7 (matrilysin).骨桥蛋白，一种基质金属蛋白酶-3（基质溶解素-1）和基质金属蛋白酶-7（基质溶素）的新型底物。
J Biol Chem. 2001 Jul 27;276(30):28261-7. doi: 10.1074/jbc.M103608200. Epub 2001 May 25.
3
The differential amino acid requirement within osteopontin in alpha4 and alpha9 integrin-mediated cell binding and migration.骨桥蛋白中α4和α9整合素介导的细胞黏附与迁移过程中的氨基酸差异需求。
Matrix Biol. 2009 Jan;28(1):11-9. doi: 10.1016/j.matbio.2008.10.002. Epub 2008 Oct 30.
4
Expression and characterization of recombinant osteopontin peptides representing matrix metalloproteinase proteolytic fragments.代表基质金属蛋白酶蛋白水解片段的重组骨桥蛋白肽的表达与特性分析
Matrix Biol. 2004 Nov;23(7):457-66. doi: 10.1016/j.matbio.2004.09.003.
5
Polymeric osteopontin employs integrin alpha9beta1 as a receptor and attracts neutrophils by presenting a de novo binding site.聚合骨桥蛋白以整合素α9β1作为受体，并通过呈现一个新的结合位点来吸引中性粒细胞。
J Biol Chem. 2009 May 29;284(22):14769-76. doi: 10.1074/jbc.M901515200. Epub 2009 Apr 3.
6
Distinct structural requirements for binding of the integrins alphavbeta6, alphavbeta3, alphavbeta5, alpha5beta1 and alpha9beta1 to osteopontin.整合素αvβ6、αvβ3、αvβ5、α5β1和α9β1与骨桥蛋白结合的不同结构要求。
Matrix Biol. 2005 Sep;24(6):418-27. doi: 10.1016/j.matbio.2005.05.005.
7
SVVYGLR motif of the thrombin-cleaved N-terminal osteopontin fragment enhances the synthesis of collagen type III in myocardial fibrosis.凝血酶切割的骨桥蛋白N端片段的SVVYGLR基序增强心肌纤维化中III型胶原的合成。
Mol Cell Biochem. 2015 Oct;408(1-2):191-203. doi: 10.1007/s11010-015-2495-y. Epub 2015 Jun 27.
8
NMR characterization of intramolecular interaction of osteopontin, an intrinsically disordered protein with cryptic integrin-binding motifs.利用 NMR 技术对具有潜在整合素结合模体的无序蛋白骨桥蛋白的分子内相互作用进行表征。
Biochem Biophys Res Commun. 2010 Mar 12;393(3):487-91. doi: 10.1016/j.bbrc.2010.02.030. Epub 2010 Feb 10.
9
Osteopontin is cleaved at multiple sites close to its integrin-binding motifs in milk and is a novel substrate for plasmin and cathepsin D.骨桥蛋白在乳中靠近整合素结合基序的多个位点被切割，是纤溶酶和组织蛋白酶 D 的新型底物。
J Biol Chem. 2010 Mar 12;285(11):7929-37. doi: 10.1074/jbc.M109.075010. Epub 2010 Jan 13.
10
Methods to Investigate Thrombin Cleavage of Osteopontin (OPN).研究凝血酶对骨桥蛋白（OPN）裂解的方法。
Methods Mol Biol. 2024;2747:95-117. doi: 10.1007/978-1-0716-3589-6_9.

引用本文的文献

1
Dynamics of Matricellular Protein Levels in Blood Predict Recovery in Patients with Human Immunodeficiency Virus-Tuberculosis Coinfection.基质细胞蛋白水平在血液中的动态变化可预测人类免疫缺陷病毒-结核病合并感染患者的恢复情况。
Viruses. 2024 Apr 24;16(5):664. doi: 10.3390/v16050664.
2
Immunoregulatory Roles of Osteopontin in Diseases.骨桥蛋白在疾病中的免疫调节作用。
Nutrients. 2024 Jan 20;16(2):312. doi: 10.3390/nu16020312.
3
Angiogenesis in the Outer Membrane of Chronic Subdural Hematomas through Thrombin-Cleaved Osteopontin and the Integrin α9 and Integrin β1 Signaling Pathways.

本文引用的文献

1
Osteopontin undergoes polymerization in vivo and gains chemotactic activity for neutrophils mediated by integrin alpha9beta1.骨桥蛋白在体内发生聚合，并通过整合素 α9β1 获得对中性粒细胞的趋化活性。
J Biol Chem. 2011 Apr 1;286(13):11170-8. doi: 10.1074/jbc.M110.189258. Epub 2011 Feb 14.
2
Thrombin-activatable carboxypeptidase B cleavage of osteopontin regulates neutrophil survival and synoviocyte binding in rheumatoid arthritis.凝血酶激活的羧肽酶B对骨桥蛋白的切割调节类风湿关节炎中中性粒细胞的存活和滑膜细胞结合。
Arthritis Rheum. 2009 Oct;60(10):2902-12. doi: 10.1002/art.24814.
3
Alpha9 integrin and its ligands constitute critical joint microenvironments for development of autoimmune arthritis.
慢性硬膜下血肿外膜中通过凝血酶切割的骨桥蛋白及整合素α9和整合素β1信号通路的血管生成
Biomedicines. 2023 May 13;11(5):1440. doi: 10.3390/biomedicines11051440.
4
MMP-3-mediated cleavage of OPN is involved in copper oxide nanoparticle-induced activation of fibroblasts.MMP-3 介导的 OPN 裂解参与了氧化铜纳米颗粒诱导的成纤维细胞激活。
Part Fibre Toxicol. 2023 May 22;20(1):22. doi: 10.1186/s12989-023-00532-y.
5
Mechanistic Insights into the Role of OPN in Mediating Brain Damage via Triggering Lysosomal Damage in Microglia/Macrophage.OPN 通过触发小胶质细胞/巨噬细胞溶酶体损伤介导脑损伤的作用机制研究
Cells. 2023 Mar 9;12(6):854. doi: 10.3390/cells12060854.
6
Osteopontin in autoimmune disorders: current knowledge and future perspective.自身免疫性疾病中的骨桥蛋白：当前的认识和未来的展望。
Inflammopharmacology. 2022 Apr;30(2):385-396. doi: 10.1007/s10787-022-00932-0. Epub 2022 Mar 2.
7
Both Full-Length and Protease-Cleaved Products of Osteopontin Are Elevated in Infectious Diseases.骨桥蛋白的全长产物和蛋白酶切割产物在传染病中均升高。
Biomedicines. 2021 Aug 13;9(8):1006. doi: 10.3390/biomedicines9081006.
8
High Levels of the Cleaved Form of Galectin-9 and Osteopontin in the Plasma Are Associated with Inflammatory Markers That Reflect the Severity of COVID-19 Pneumonia.血浆中半乳糖凝集素-9 和骨桥蛋白的高水平与反映 COVID-19 肺炎严重程度的炎症标志物相关。
Int J Mol Sci. 2021 May 7;22(9):4978. doi: 10.3390/ijms22094978.
9
Integrin α9 regulates smooth muscle cell phenotype switching and vascular remodeling.整合素 α9 调节平滑肌细胞表型转换和血管重塑。
JCI Insight. 2021 May 24;6(10):147134. doi: 10.1172/jci.insight.147134.
10
Degeneration of Aortic Valves in a Bioreactor System with Pulsatile Flow.具有脉动流的生物反应器系统中主动脉瓣的退变
Biomedicines. 2021 Apr 23;9(5):462. doi: 10.3390/biomedicines9050462.
α9整合素及其配体构成了自身免疫性关节炎发展的关键关节微环境。
J Immunol. 2009 Jun 15;182(12):8015-25. doi: 10.4049/jimmunol.0900725.
4
Polymeric osteopontin employs integrin alpha9beta1 as a receptor and attracts neutrophils by presenting a de novo binding site.聚合骨桥蛋白以整合素α9β1作为受体，并通过呈现一个新的结合位点来吸引中性粒细胞。
J Biol Chem. 2009 May 29;284(22):14769-76. doi: 10.1074/jbc.M901515200. Epub 2009 Apr 3.
5
The differential amino acid requirement within osteopontin in alpha4 and alpha9 integrin-mediated cell binding and migration.骨桥蛋白中α4和α9整合素介导的细胞黏附与迁移过程中的氨基酸差异需求。
Matrix Biol. 2009 Jan;28(1):11-9. doi: 10.1016/j.matbio.2008.10.002. Epub 2008 Oct 30.
6
Syndecan-4 protects against osteopontin-mediated acute hepatic injury by masking functional domains of osteopontin.Syndecan-4通过掩盖骨桥蛋白的功能域来保护机体免受骨桥蛋白介导的急性肝损伤。
J Exp Med. 2008 Jan 21;205(1):25-33. doi: 10.1084/jem.20071324. Epub 2007 Dec 24.
7
Transglutaminase 2 in inflammation.炎症中的转谷氨酰胺酶2
Front Biosci. 2006 Sep 1;11:3026-35. doi: 10.2741/2030.
8
Expression and characterization of recombinant osteopontin peptides representing matrix metalloproteinase proteolytic fragments.代表基质金属蛋白酶蛋白水解片段的重组骨桥蛋白肽的表达与特性分析
Matrix Biol. 2004 Nov;23(7):457-66. doi: 10.1016/j.matbio.2004.09.003.
9
Osteopontin as a mediator of NKT cell function in T cell-mediated liver diseases.骨桥蛋白作为T细胞介导的肝脏疾病中NKT细胞功能的介质。
Immunity. 2004 Oct;21(4):539-50. doi: 10.1016/j.immuni.2004.08.012.
10
Essential role of the cryptic epitope SLAYGLR within osteopontin in a murine model of rheumatoid arthritis.在类风湿性关节炎小鼠模型中，骨桥蛋白内隐蔽表位SLAYGLR的重要作用。
J Clin Invest. 2003 Jul;112(2):181-8. doi: 10.1172/JCI17778.