Interactive Signaling Modules in Vascular Inflammation

血管炎症中的交互式信号模块

• 批准号: 8467009
• 负责人: LINDA H SHAPIRO
• 金额: $ 161.31万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8467009
• 关键词: Adhesions; Adhesives; Adult; Affect; Age; Animal Model; Apoptosis; Apoptotic; Area; Arterial Fatty Streak; Atherosclerosis; Biochemical; Biochemistry; Biological; Biological Process; Biology; Blood Vessels; Cardiovascular Diseases; Cause of Death; Cell Communication; Cell physiology; Cell surface; Cells; Cellular biology; Cessation of life; Chronic; Clear Cell; Coagulation Process; Complex; Connecticut; Consensus; Coupled; Dengue Hemorrhagic Fever; Development; Diabetes Mellitus; Diagnostic; Discipline; Disease; Economic Burden; Elderly; Elements; Endothelial Cells; Endothelium; Environment; Essential Hypertension; Event; Foam Cells; Fostering; Functional disorder; GTP-Binding Proteins; Genetic; Goals; Health; Health Expenditures; Heart Diseases; Hematopoietic; Histology; Home environment; Homing; Human; Immune; Incidence; Inflammation; Inflammatory; Integrins; Investigation; Ischemia; Knowledge; Lead; Lesion; Lipids; Lupus; Molecular; Morbidity - disease rate; Mus; Myeloid Cells; Myocardial Infarction; Natural Killer Cells; Neoplasm Metastasis; Neuropathy; Obstruction; Organism; Pathogenesis; Pathologic; Pathology; Pathway interactions; Pharmacologic Substance; Phenotype; Physiological; Physiology; Prevention; Process; Program Research Project Grants; Receptor Signaling; Regulation; Research; Research Personnel; Retinal Diseases; Rheumatoid Arthritis; Risk Factors; Role; Rupture; Sepsis; Signal Pathway; Signal Transduction; Signal Transduction Pathway; Stroke; System; T-Lymphocyte; Technology; Therapeutic; Thrombosis; Tissues; Translations; Tyrosine Phosphorylation; United States; Universities; Vascular Endothelial Cell; Vascular System; Woman; alanine aminopeptidase; atherogenesis; autoimmune vasculitis; base; blood glucose regulation; blood lipid; body system; cell behavior; cell injury; cell motility; cell type; cytokine; fluorescence imaging; in vivo; inhibitor/antagonist; insight; interdisciplinary approach; interest; investigator training; macrophage; mast cell; migration; molecular pathology; monocyte; mortality; mouse model; multidisciplinary; novel; novel strategies; novel therapeutics; oncology; premature; programs; protein activation; sex; sphingosine 1-phosphate; therapeutic development; transplant associated vasculopathy; vascular inflammation

The competitive renewal of the program project application "Interactive signaling modules in vascular inflammation" is focused on the process of inflammatory changes in the vessel wall that lead to atherosclerosis. The program brings together seven independent investigators interested in the vascular biology. The theme of the program is to define molecular mechanisms important for pathologic inflammatory events with a focus on myeloid cells. The central hypothesis is that interactions between distinct signal transduction modules influence fundamental cellular processes such as cell-cell interaction, cell migration, inflammation, death and engulfment of apoptotic cells, ultimately altering the pathogenesis and progression of atherosclerosis. Each project in the program focuses on a unique aspect of the theme to advance our understanding of inflammatory vascular phenotypes. Project 1 (Hla) proposes to investigate the role of sphingosine 1-phosphate on macrophage inflammasome function and atherogenesis. This project shares several common interests with Project 2 (Wu), which is focused on PLCB regulation of macrophage apoptosis and atherogenesis. Project 3 (Han) focuses on the process of cell-cell recognition process by which apoptotic cells are cleared from the vascular wall. Thus, this project has common interests as projects 2 and 4. Project 4 (Shapiro) focuses on the novel role of the cell-surface molecule CD13 in the adhesion of myeloid cells to vascular endothelial cells, and explores this mechanism in vascular pathology. All the projects utilize molecular, biochemical, cell biological and in vivo mouse models. Thus three cores, administrative, fluorescence imaging and vascular histology and atherosclerosis are proposed to support the projects with state-of-the-art technology. All the projects and cores interact and mutually reinforce each other to achieve the goals of the program in a synergistic manner. Coupled with strong institutional support to the Center for Vascular Biology, it is anticipated that significant new insights on vascular inflammation and atherosclerosis will be forthcoming from this renewal program project application.

该计划项目申请的竞争性续签《血管炎症中的交互信号模块》聚焦于导致动脉粥样硬化的血管壁炎症变化的过程。该项目汇集了七名对血管生物学感兴趣的独立研究人员。该计划的主题是确定对病理性炎症事件重要的分子机制，重点是髓系细胞。中心假设是不同信号转导模块之间的相互作用影响基本的细胞过程，如细胞-细胞相互作用、细胞迁移、炎症、死亡和吞噬凋亡细胞，最终改变动脉粥样硬化的发病和进展。该计划中的每个项目都集中在主题的一个独特方面，以促进我们对炎症性血管表型的理解。项目1(人类白细胞抗原)建议研究1-磷酸鞘氨醇在巨噬细胞炎症体功能和动脉粥样硬化形成中的作用。这个项目与项目2(WU)有几个共同的兴趣，该项目的重点是PLCB对巨噬细胞凋亡和动脉粥样硬化的调节。项目3(HAN)专注于细胞-细胞识别过程，通过细胞识别过程将凋亡细胞从血管壁中清除。因此，本项目与项目2和项目4有共同的兴趣。项目4(Shapiro)专注于细胞表面分子CD13在髓系细胞与血管内皮细胞黏附中的新作用，并探讨了这一机制在血管病理学中的作用。所有这些项目都利用了分子、生化、细胞生物学和活体小鼠模型。因此，提出了行政、荧光成像和血管组织学与动脉粥样硬化三个核心，以支持具有最先进技术的项目。所有项目和核心相互作用，相互加强，以协同的方式实现方案的目标。加上对血管生物学中心的强有力的机构支持，预计这一更新计划项目的申请将对血管炎症和动脉粥样硬化有重要的新见解。

项目成果

CD13 restricts TLR4 endocytic signal transduction in inflammation.

• DOI: 10.4049/jimmunol.1403133
• 发表时间: 2015-05-01
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Ghosh M;Subramani J;Rahman MM;Shapiro LH
• 通讯作者: Shapiro LH

Defective sphingosine 1-phosphate receptor 1 (S1P1) phosphorylation exacerbates TH17-mediated autoimmune neuroinflammation.

• DOI: 10.1038/ni.2730
• 发表时间: 2013-11
• 期刊: Nature immunology
• 影响因子: 30.5

Regulation of mammalian physiology, development, and disease by the sphingosine 1-phosphate and lysophosphatidic acid receptors.

• DOI: 10.1021/cr200273u
• 发表时间: 2011-10-12
• 期刊: CHEMICAL REVIEWS
• 影响因子: 62.1
• 作者: Blaho, Victoria A.;Hla, Timothy
• 通讯作者: Hla, Timothy

CD13 promotes mesenchymal stem cell-mediated regeneration of ischemic muscle.

• DOI: 10.3389/fphys.2013.00402
• 发表时间: 2014
• 期刊: Frontiers in physiology
• 影响因子: 4
• 作者: Rahman MM;Subramani J;Ghosh M;Denninger JK;Takeda K;Fong GH;Carlson ME;Shapiro LH
• 通讯作者: Shapiro LH

In vitro Ag Cross-presentation and in vivo Ag Cross-presentation by Dendritic Cells in the Mouse.

• DOI: 10.21769/bioprotoc.305
• 发表时间: 2012-12-20
• 期刊: Bio-protocol
• 影响因子: 0.8
• 作者: Ghosh M;Shapiro LH
• 通讯作者: Shapiro LH