COLLAGEN METABOLISM IN WOUND REPAIR AND KELOID

伤口修复和疤痕疙瘩中的胶原蛋白代谢

• 批准号: 2518880
• 负责人: IRWIN KELMAN COHEN
• 金额: $ 29.96万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1976
• 资助国家: 美国
• 起止时间: 1976-12-01 至 2001-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2518880
• 关键词: RNase protection assay; angiogenesis; biological signal transduction; biopsy; cellular pathology; collagen; collagenase; connective tissue metabolism; enzyme activity; enzyme linked immunosorbent assay; exudate /transudate; fibrosis; high performance liquid chromatography; histopathology; human subject; immunocytochemistry; in situ hybridization; inflammation; keloid skin disorder; protein biosynthesis; protein degradation; scars; tissue /cell culture; western blottings; wound healing

DESCRIPTION: (Adapted from the applicant's abstract) Although animal models and in vitro systems have been very useful in the past to gain insight into the cellular, biochemical and molecular events during tissue repair, these systems have limitations when addressing the unique clinical problems associated with human wound healing. The human response encompasses a wide spectrum of healing phenomena with overhealing and fibrosis on one end and chronic ulcer formation on the other end. Animals do not develop excessive scar issue nor do they manifest problems with deficient healing. Therefore, this project is designed to characterize and analyze the normal wound healing response in humans as well as the pathologic responses seen at opposite ends of the spectrum. The human keloid will represent conditions of fibrosis whereas chronic non-healing diabetic ulcers will serve as a model of deficient healing. All studies will be done in humans using the normally available wound exudates, biopsies, and excised tissue following normally scheduled surgical treatments for these patients. In addition, an implantable tube consisting of an expanded form of Teflon, called Impra, has proven to be useful to collect new wound tissue for analysis. This laboratory has now developed and adapted state-of-the-art technologies and methods to study human wound healing. Therefore, these strategies will be employed to analyze inflammation, cytokine production, matrix synthesis and degradation, angiogenesis and contraction in normal human wounds, keloids and chronic non- healing ulcers. The laboratory methods include routine histology, immunostaining, ELISA assays, in situ hybridization, RNase protection assays, a new collagen radiolabeled substrate assay to quantify collagenase and gelatinase activity, HPLC quantitation of hydroxyproline and leucine deposition, and Western blot analysis. These methods have been modified to be applicable to analyze the small amounts of tissue and exudate material that can be obtained from these human sources. These studies will compare and contrast the normal mechanisms responsible for healing in healthy tissue to those mechanisms responsible for overhealing in keloids and underhealing in chronic ulcers.

描述：（改编自申请人的摘要），尽管动物 模型和体外系统过去非常有用 深入了解细胞，生化和分子事件 组织修复，这些系统在解决唯一 与人伤口愈合相关的临床问题。人类 反应包括 一端的过度感染和纤维化，以及在慢性溃疡上形成 另一端。动物不会出现过多的疤痕问题，也不会 表现出缺乏治愈的问题。因此，这个项目是 旨在表征和分析正常伤口愈合反应 在人类以及在相反的病理反应中 频谱。人乳突将代表纤维化的条件 而慢性非治疗糖尿病性溃疡将成为 不足的康复。所有研究将在人类中使用 通常可用的伤口渗出，活检和切除的组织 通常针对这些患者进行外科手术治疗。 另外，一个可植入的管，由扩展的形式组成 Teflon被称为Impa，被证明可用于收集新伤口 组织进行分析。该实验室现已发展并适应 研究人伤口愈合的最先进技术和方法。 因此，将采用这些策略来分析炎症， 细胞因子产生，基质合成和降解，血管生成和 正常人伤口，酮脚轮和慢性非愈合的收缩 溃疡。实验室方法包括常规的组织学， 免疫染色，ELISA测定，原位杂交，RNase保护 测定，一种新的胶原蛋白放射标记的底物测定，以量化 胶原酶和明胶活性，HPLC羟丙烯的定量 和亮氨酸沉积和蛋白质印迹分析。这些方法具有 被修改以适用于分析少量组织 并散发出可以从这些人类来源获得的材料。 这些研究将比较和对比正常机制 负责在健康组织中愈合到这些机制 负责过度旋转乳子状和慢性疾病 溃疡。