Hyaluronan Matrices in Vascular Pathologies

血管病理学中的透明质酸基质

• 批准号: 8494077
• 负责人: VINCENT CHARLES HASCALL
• 金额: $ 217.54万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-07-01 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8494077
• 关键词: Adenosine; Adhesives; Anabolism; Authorship; Blood Platelets; Blood Vessels; Carbohydrates; Cell membrane; Cells; Cellular Stress; Chondroitin Sulfates; Clinical Pathology; Collaborations; Complex; Core Protein; Cytosol; Development; Diabetes Mellitus; Excision; Extracellular Space; Functional disorder; Future; Glucose; Glycocalyx; Glycosaminoglycans; Goals; Golgi Apparatus; Heparin; Heparitin Sulfate; Hyaluronan; Hyperglycemia; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Investigation; Keratan Sulfate; Leadership; Leukocytes; Medical Students; Methods; Modification; Paper; Pathology; Pathway interactions; Postdoctoral Fellow; Process; Proteoglycan; Pulmonary Hypertension; Recruitment Activity; Research; Research Personnel; Resource Sharing; Role; Signal Transduction; Staining method; Stains; Structure; Techniques; Tissues; Training; Uncertainty; Universities; Uridine Diphosphate Sugars; Vascular Diseases; Visit; Work; Wound Healing; base; diabetic; frontier; graduate student; hyaluronan synthase 1; macrophage; meetings; member; monocyte; novel; programs; research study; response; skills; sugar

DESCRIPTION (provided by applicant): (Overview, Hascall) Program Introduction and Objectives - The 5 projects in our PEG, Hyaluronan Matrices in Vascular Pathologies, explore the emerging central role that hyaluronan (HA)-based matrices have in vascular development and inflammatory pathologies of the vasculature. Members of the Research Team have already collaborated and pioneered the initial research with this matrix and its dialogue with inflammatory cells. We now propose to focus in depth on novel investigations that further investigate the HA matrix and its interactions with leukocytes in vasculopathies related to diabetes (Project 1), wound healing (Project 2), inflammatory bowel disease (Project 3), pulmonary hypertension (Project 4), and glycocalyx/pericellular matrix modification in vascular development (Project 5). The existing synergy of the Research Team is established by the co-authorship of papers in the biosketches, by new collaborations, and by the crosstalk between the aims of the projects and the methods employed. During the course of the PEG, each project will recruit two junior investigators (graduate student, medical student, or postdoctoral fellow) who will receive glycoscience and glycotechnology training through the enrichment course described in the Glycosciences Skills Development Core C and by attending courses at the Complex Carbohydrate Research Center at the University of Georgia. Shared Resource Core B will provide all projects with comprehensive analyses to determine the amounts, sizes, fine structures, and modifications of glycosaminoglycans, and will prepare tissues for sectioning and staining for HA and relevant matrix molecules. Shared Resource Core B will work with Glycosciences Skills Development Core C to provide training for the junior investigators in these techniques with emphasis on their project-related experiments. The Administration Core will provide overall leadership for the PEG and coordinate the biweekly meetings of the investigators in the Research Teams to discuss ongoing experimental results and plan future experiments. Biannual meetings of the Internal Advisory Board, and visits by the Visiting Scholars and members of an External Advisory Board will review progress, provide project guidance, and enrich scholarly activities within the PEG. RELEVANCE: Vascular tissues and circulating leukocytes are involved in essentially all inflammatory processes. Thus, understanding the mechanisms involved in synthesizing the monocyte-adhesive hyaluronan matrix and the responses of inflammatory cells that interact with it, offers to provide a central paradigm for most inflammatory processes and subsequent pathologies.

概述（由申请人提供）项目介绍和目标-我们的PEG中的5个项目，血管病理学中的透明质酸基质，探索基于透明质酸（HA）的基质在血管发育和血管炎症病理中的新兴中心作用。研究小组的成员已经合作并开创了这种基质及其与炎症细胞对话的初步研究。我们现在建议深入研究新的研究，进一步研究HA基质及其与白细胞在与糖尿病（项目1）、伤口愈合（项目2）、炎症性肠病（项目3）、肺动脉高压（项目4）和血管发育中的糖萼/细胞周围基质修饰（项目5）相关的血管病变中的相互作用。研究小组现有的协同作用是通过共同撰写生物草图的论文，通过新的合作，以及通过项目目标和所采用的方法之间的相互交流来建立的。在PEG期间，每个项目将招募两名初级研究人员（研究生、医学院学生或博士后），他们将通过糖科学技能发展核心C中描述的浓缩课程和参加乔治亚大学复合碳水化合物研究中心的课程接受糖科学和糖技术培训。共享资源核心B将为所有项目提供全面的分析，以确定糖胺聚糖的数量、大小、精细结构和修饰，并为HA和相关基质分子准备切片和染色的组织。共享资源核心B将与糖苷科学技能开发核心C合作，为初级研究人员提供这些技术的培训，重点是他们的项目相关实验。行政核心将为PEG提供全面领导，并协调研究小组的研究人员每两周举行一次会议，讨论正在进行的实验结果并规划未来的实验。一年两次的内部咨询委员会会议，以及访问学者和外部咨询委员会成员的访问，将审查PEG的进展，提供项目指导，并丰富PEG的学术活动。相关性：血管组织和循环白细胞基本上参与所有炎症过程。因此，了解单核细胞黏附透明质酸基质的合成机制以及与之相互作用的炎症细胞的反应，为大多数炎症过程和随后的病理提供了一个中心范式。