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: 3269988
• 负责人: IRWIN KELMAN COHEN
• 金额: $ 26.79万
• 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 1995-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3269988
• 关键词: athymic mouse; cell population study; cellular pathology; collagen; collagenase; connective tissue metabolism; disease /disorder model; extracellular matrix; fibroblast growth factor; fibroblasts; fibrosis; flow cytometry; genetic transcription; growth factor receptors; human tissue; implant; in situ hybridization; keloid skin disorder; laboratory rat; malnutrition; mast cell; monocyte; physiologic stressor; platelet derived growth factor; polymerase chain reaction; prednisolone; protein biosynthesis; scars; skin transplantation; tissue /cell culture; transforming growth factors; tumor necrosis factor alpha; western blottings; wound healing

The long-term objective of this project is to define and analyze the cellular interactions and molecular mechanisms involved in the regulation of collagen metabolism during tissue repair. This objective will be met by biochemically characterizing fibroblast subpopulations derived from normal dermis, scar, and keloids with respect to collagen synthesis, collagenase expression and TGFbeta receptor number and affinities. These studies test the hypothesis that fibrosis is the result of a selection of fibroblast subpopulations capable of producing increased amounts of collagen. In addition, ongoing studies will be completed to identify the collagen-producing monocytes observed during the early phase of wound repair. This specific population of cells will then be eliminated from the wound site to determine its physiological significance during tissue repair. In other studies, the amount of mRNA for collagens, fibronectin, collagenase and TGFbeta will be quantitated in normal and biologically compromised rat wounds to examine transcriptional control mechanisms during tissue repair. This information will be correlated with the actual expression of these proteins as quantitated using Western blot analysis of wound fluid and tissue extracts as well as immunohistochemical localization. In addition, collagenase will be quantitated to determine the role of collagen degradation in the net amount of collagen deposited in a wound site. The amount of collagenase mRNA will then be correlated with enzyme activity to analyze the mechanism of enzyme regulation. Keloid explants will be placed onto athymic nude mice to study collagen metabolism in vivo using oxygen-18 labeling techniques. This will allow a study of the dynamics of keloid pathogenesis in vivo and provide initial data for eventual in vivo human studies. This animal model should also prove useful for evaluation of pharmacologic agents to treat keloids. The probable role of the mast cell and tumor necrosis factor (TN-F) in keloid formation will be examined both in the athymic nude mouse model as well as in cell culture. The net result of these studies will be a better understanding of the molecular mechanisms which regulate normal wound repair and how these regulatory events are altered in abnormal repair.

该项目的长期目标是定义和分析 涉及调节的细胞相互作用和分子机制 组织修复期间胶原蛋白代谢的。这个目标将由 生物化学表征源自正常的成纤维细胞亚群 关于胶原蛋白合成，胶原酶，真皮，疤痕和酮 表达和TGFBETA受体数量和亲和力。这些研究测试 纤维化是成纤维细胞选择的结果的假设 能够产生增加胶原蛋白的亚群。在 此外，正在进行的研究将完成，以确定 在伤口早期观察到的产生胶原蛋白的单核细胞 维修。然后将从 伤口部位确定其在组织中的生理意义 维修。在其他研究中，胶原蛋白的mRNA量，纤连蛋白， 胶原酶和TGFBETA将在正常和生物学上进行定量 大鼠伤口受损，以检查转录控制机制 组织修复。此信息将与实际的 这些蛋白质的表达是使用Western印迹分析定量的 伤口液和组织提取物以及免疫组织化学 本土化。另外，胶原酶将被定量以确定 胶原蛋白降解在沉积在 伤口部位。然后，胶原酶mRNA的量将与 酶活性分析酶调节的机制。瘢痕疙瘩 外植体将被放在无胸腺裸鼠上，以研究胶原蛋白代谢 使用氧气18标记技术的体内体内。这将允许研究 体内乳子状发病机理的动力学，并提供初始数据 最终的体内人类研究。该动物模型也应证明有用 用于评估药理学剂以治疗酮。可能的角色 乳突细胞和肿瘤坏死因子（TN-F）的乳突形成将会 在裸露的小鼠模型和细胞中都需要检查 文化。这些研究的最终结果将是对 调节正常伤口修复的分子机制以及如何 调节事件在异常修复中发生了改变。