OSTEOPONTIN SIGNALING--MECHANISM AND CONSEQUENCES

骨桥蛋白信号传导——机制和后果

• 批准号: 2607940
• 负责人: DAVID T DENHARDT
• 金额: $ 26.5万
• 依托单位: RUTGERS, THE STATE UNIV OF N.J.
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-15 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2607940
• 关键词: cell line; gene expression; hydrogen peroxide; hypoxia; integrins; laboratory mouse; nitric oxide; nitric oxide synthase; nuclear factor kappa beta; osteopontin; oxidative stress; receptor; receptor binding; tissue /cell culture; transcription factor

DESCRIPTION (Adapted from the Applicant's Abstract): Osteopontin (OPN) is a secreted phosphoprotein and acts both as a cytokine and cell adhesion molecule. It can facilitate cell adhesion and initiate a signaling pathway by interacting with cell surface receptors. It binds calcium and suppresses calcium salt precipitation; controls tissue mineralization and bone remodelling; it regulates certain immune functions and has an antiinfectious role; and it can protect cells from oxidant-induced cell damage perhaps by reducing H2O2. It is capable of modulating gene expression and of suppressing the induction of iNOS mRNA synthesis by inflammatory mediators. Nitric oxide is an important second message being implicated in controlling vascular tone, mediating cell killing by certain cytotoxic cells, and conveying signals in nervous system. OPN appears to be the means by which mammalian organisms regulate the production of NO. The purpose of this project is to evaluate the role of osteopontin in various processes mentioned above and how does the OPN carry out its physiological roles. Intricacies of OPN interaction with cell surface receptors and signaling pathways by which OPN alters gene expression are main areas of focus in the proposed research. In addition the role of OPN in protecting the cells from oxidant-induced injury will be investigated.

描述（改编自申请人的摘要）：骨桥骨（OPN）是一个 分泌的磷蛋白，并用作细胞因子和细胞粘附 分子。 它可以促进细胞粘附并启动信号通路 通过与细胞表面受体相互作用。 它结合钙并抑制 钙盐沉淀；控制组织矿化和骨骼 重塑；它调节某些免疫功能，并具有抗疫苗 角色;它可以保护细胞免受氧化剂诱导的细胞损害 减少H2O2。 它能够调节基因表达和 抑制炎症介质诱导iNOS mRNA合成。 一氧化氮是与控制有关的重要第二个信息 血管张力，介导某些细胞毒性细胞杀死细胞，以及 在神经系统中传达信号。 OPN似乎是 哺乳动物有机体调节NO的产生。 这个目的 项目是评估骨桥蛋白在各种过程中的作用 上面提到的以及OPN如何扮演其生理角色。 OPN与细胞表面受体和信号转导的复杂性 OPN改变基因表达是主要重点领域的途径 拟议的研究。 另外，OPN在保护细胞免受的作用 将研究氧化剂诱导的损伤。