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: 3269987
• 负责人: IRWIN KELMAN COHEN
• 金额: $ 20.08万
• 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 1990-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3269987
• 关键词: WI38 cell; antiinflammatory agents; biological models; cell cycle; cellular immunity; collagen disorder; collagenase; connective tissue development; connective tissue disorder chemotherapy; connective tissue metabolism; fibroblasts; heterozygote; histamine; human tissue; humoral immunity; immunofluorescence technique; indomethacin; keloid skin disorder; macrophage; nuclear magnetic resonance spectroscopy; nucleic acid metabolism; prednisolone; protease inhibitor; radiotracer; scars; tissue /cell culture; triamcinolone; wound healing

The long-term objective of this project is to elucidate the cellular interactions and molecular mechanisms involved in the regulation of collagen metabolism during wound repair. The objective will be met first by determining if there is a selection of specialized subpopulations of fibroblasts after wounding, each with different potentials to produce collagen. These studies may explain why certain individuals are susceptible to excessive scar formation (keloid and hypertrophic scar), while others have decreased wound healing (hernia and malnutrition). Other studies focus specifically on fibroblasts and inflammatory cell interactions to determine how these interactions modulate the extent and quality of the fibrotic reponse. These studies will be pursued using the PVA implant in animals and humans to characterize inflammatory cell dynamics as they relate to connective tissue deposition during normal wound healing and following pharmacologic modulation. Further, the possibility that inflammatory cells produce collagen in the initial wound matrix will be explored further using light and electron immunohistochemistry, biochemical analysis, and molecular probe analysis. An in vitro model of fibroplasia will be used to reconstitute the wound environment to further determine the inflammatory, cellular and humoral participants in the ultimate fibrotic response. A low molecular weight, macrophage-derived chemotactic factor for fibroblasts which we have isolated will be purified further and characterized to determine the role in fibroblast chemotaxis. Recent technological advances in molecular biology now allow investigation into the genetic regulation of collagen metabolism during wound repair. Total mRNA will be isolated from dermal wound fibroblasts, from selected subsets of fibroblasts cultured under various environmental, nutritional and pharmacologic conditions, from the in vitro fibroplasia experiments, and from inflammatory cells in reconstituted blood clots. Using cell-free protein synthesizing systems and cDNA probe analysis, the level of transcriptional or translational control can be determined in those various systems. The net result of these multifacted studies of inflammation and wound repair will be a better understanding of the steps at which collagen metabolism is regulated and specific mechanisms which can be used to better control abnormal healing.

该项目的长期目标是阐明细胞 与调节有关的相互作用和分子机制 伤口修复过程中的胶原蛋白代谢。 目标将首先实现 通过确定是否有选择的专业亚群 受伤后的成纤维细胞，每种都有不同的潜力 胶原。 这些研究可能解释了为什么某些人是 容易受到过度疤痕形成（酮和肥厚性疤痕）， 而其他人则减少了伤口愈合（疝气和营养不良）。 其他 研究专门针对成纤维细胞和炎症细胞 相互作用以确定这些相互作用如何调节程度和 纤维化物质的质量。 这些研究将使用 在动物和人类中植入PVA以表征炎症细胞 在正常伤口期间与结缔组织沉积有关的动力学 愈合并遵循药理调节。 此外，可能性 炎性细胞在最初的伤口基质中产生胶原蛋白会 使用光和电子免疫组织化学进一步探索 生化分析和分子探针分析。 体外模型的 纤维化将用于重建伤口环境以进一步 确定炎症性，细胞和体液参与者 最终的纤维化反应。 低分子量，巨噬细胞的衍生 我们已经分离的成纤维细胞的趋化因子将被纯化 进一步并表征以确定成纤维细胞趋化性的作用。 分子生物学的最新技术进步现在允许研究 在伤口修复过程中胶原蛋白代谢的遗传调节。 总mRNA将从精美的成纤维细胞中分离出来，从选定的 在各种环境，营养中培养的成纤维细胞子集 和药理学条件，来自体外纤维状实验， 来自重建的血凝块中的炎症细胞。 使用无细胞 蛋白质合成系统和cDNA探针分析，水平 转录或翻译控制可以在各种不同 系统。 这些多因素炎症和 伤口修复将更好地理解胶原蛋白的步骤 代谢是受调节的，可以用来改善的特定机制 控制异常愈合。