Hyaluronan Matrices in Vascular Pathologies

血管病理学中的透明质酸基质

• 批准号: 8856310
• 负责人: VINCENT CHARLES HASCALL
• 金额: $ 219.63万
• 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 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8856310
• 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.

描述（由申请人提供）：（概述，Hascall）项目简介和目标-我们的PEG（血管病理学中的透明质酸基质）中的5个项目探索了基于透明质酸（HA）的基质在血管发育和血管系统炎症病理学中的新兴核心作用。研究团队的成员已经合作并率先使用该基质及其与炎症细胞的对话进行了初步研究。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糖尿病相关血管病变（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/细胞周基质修饰（项目5）中的相互作用。研究团队现有的协同作用是通过在bisketches中共同撰写论文，通过新的合作，以及通过项目目标和所采用方法之间的串扰建立的。在PEG过程中，每个项目将招募两名初级研究者（研究生、医学生或博士后研究员），他们将通过糖科学技能发展核心C中描述的丰富课程和参加格鲁吉亚大学复杂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分析，以确定糖胺聚糖的数量、大小、精细结构和修饰，并将制备用于切片和HA及相关基质分子染色的组织。共享资源核心B将与糖科学技能发展核心C合作，为初级研究者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，并协调研究团队中研究人员的双周会议，以讨论正在进行的实验结果并计划未来的实验。内部咨询委员会一年两次的会议，以及访问学者和外部咨询委员会成员的访问将审查进展情况，提供项目指导，并丰富PEG内的学术活动。相关性：血管组织和循环白细胞参与基本上所有的炎症过程。因此，了解参与合成单核细胞粘附性透明质酸基质的机制以及与其相互作用的炎性细胞的反应，为大多数炎性过程和随后的病理提供了一个中心范例。