Role of wound provisional matrix in endothelial function

伤口临时基质在内皮功能中的作用

• 批准号: 7371086
• 负责人: Henry C Hsia
• 金额: $ 13万
• 依托单位: UNIV OF MED/DENT NJ-R W JOHNSON MED SCH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7371086
• 关键词: Adenovirus Vector; Affect; Award; Binding; Biology; Blood Vessels; Blood capillaries; Burn injury; Cell Adhesion; Cell physiology; Cells; Chronic; Cicatrix; Clinical; Coagulation Process; Coculture Techniques; Complement; Condition; Culture Techniques; Deposition; Development; Disease; ECM receptor; Embryonic Development; Endothelial Cells; Extracellular Matrix; Extracellular Matrix Proteins; Fibrin; Fibroblasts; Fibronectins; Future; Gel; Goals; Human; Injury; Integrins; Investigation; Laboratories; Mentored Clinical Scientist Development Award (K08); Modeling; Molecular; Morphogenesis; Morphology; Phase; Physicians; Plastic Surgical Procedures; Play; Process; Proteins; Rate; Receptor Cell; Recruitment Activity; Research; Research Personnel; Role; Scientist; Signal Transduction; Staging; Structure; System; Tenascin; Testing; Therapeutic; Tissues; Training; Tube; Ulcer; Vacuole; Work; Wound Healing; base; capillary; cell behavior; experience; in vitro Model; in vivo; novel; programs; receptor; research study; response; response to injury; skills; wound

DESCRIPTION (provided by applicant): The candidate plans to be a physician-scientist with the immediate goal of complementing his clinical experience in plastic surgery with rigorous scientific training and the long-term goal of making significant contributions to our. understanding of molecular mechanisms underlying the wound repair process. To achieve this, a 2-phase career development plan is proposed which allows the candidate to transition over a 5-year period from supervised research and coursework to independent investigations incorporating clinical perspectives. The candidate will develop research skills through the following proposed project. Wound repair begins with the fibrin clot, which acts as a provisional extracellular matrix (ECM) that recruits necessary cells for wound healing. CelI-ECM interactions play a critical role in wound cell function. This proposal will examine their contributions to endothelial cell function and capillary formation. Fibrin gels are routinely used in tube formation studies. An in vitro model of the wound provisional matrix based on a three-dimensional (3D) fibrin gel and allowing incorporation of fibronectin (FN) and other ECM proteins will be used to determine the roles of FN and tenascin-C, important components of the wound matrix, in controlling endothelial cell reorganization into 3D tube structures. To be tested are the following hypotheses: 1) the presence of FN in fibrin matrices is essential for capillary tube morphogenesis, 2) tenascin-C modulates the assembly of capillary tube networks in 3D fibrin-FN matrices by affecting celI-FN interactions, and 3) blood vessel formation modulated by FN and tenascin-C plays a significant role in abnormal scar formation. These experiments will contribute to our understanding of the role of the ECM in endothelial cell function and their contributions to the tissue response to injury. An ultimate goal is the development of more effective therapeutic strategies for conditions resulting from injury such as burns.

描述（由申请人提供）： 候选人计划成为一名医师科学家，近期目标是通过严格的科学训练补充他在整形外科方面的临床经验，长期目标是为我们的整形外科做出重大贡献。了解伤口修复过程的分子机制。为了实现这一目标，提出了一个两阶段的职业发展计划，该计划允许候选人在 5 年的时间内从监督研究和课程作业过渡到结合临床观点的独立调查。候选人将通过以下拟议项目培养研究技能。 伤口修复始于纤维蛋白凝块，它充当临时细胞外基质 (ECM)，招募伤口愈合所需的细胞。 CelI-ECM 相互作用在伤口细胞功能中发挥着关键作用。该提案将检查它们对内皮细胞功能和毛细血管形成的贡献。纤维蛋白凝胶通常用于管形成研究。基于三维 (3D) 纤维蛋白凝胶并允许掺入纤连蛋白 (FN) 和其他 ECM 蛋白的伤​​口临时基质体外模型将用于确定 FN 和生腱蛋白-C（伤口基质的重要成分）在控制内皮细胞重组为 3D 管结构中的作用。待测试的是以下假设：1) 纤维蛋白基质中 FN 的存在对于毛细管形态发生至关重要，2) 生腱蛋白-C 通过影响细胞-FN 相互作用来调节 3D 纤维蛋白-FN 基质中毛细管网络的组装，3) 由 FN 和生腱蛋白-C 调节的血管形成在异常疤痕形成中发挥重要作用。这些实验将有助于我们了解 ECM 在内皮细胞功能中的作用及其对组织损伤反应的贡献。最终目标是针对烧伤等损伤引起的疾病制定更有效的治疗策略。