COLLAGEN METABOLISM IN WOUND REPAIR AND KELOID

这个项目的长期目标是阐明细胞 参与调节的相互作用和分子机制 胶原蛋白代谢过程中的创伤修复。 目标将首先实现 通过确定是否有选择的专门亚群， 成纤维细胞受伤后，每一个不同的潜力，以产生 胶原 这些研究可以解释为什么某些人 容易形成过多的瘢痕（瘢痕疙瘩和增生性瘢痕）， 而其他人则减少了伤口愈合（疝气和营养不良）。 其他 研究特别关注成纤维细胞和炎性细胞 相互作用以确定这些相互作用如何调节程度和 纤维化反应的质量。 这些研究将使用 PVA植入动物和人体以表征炎性细胞 与正常伤口期间结缔组织沉积相关的动力学 愈合和随后的药理学调节。 此外， 炎症细胞在最初的伤口基质中产生胶原蛋白， 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。 的体外模型 纤维组织增生将用于重建伤口环境， 确定炎症，细胞和体液参与者， 最终纤维化反应。 一种低分子量巨噬细胞衍生的 我们分离的成纤维细胞趋化因子将被纯化 进一步表征以确定其在成纤维细胞趋化性中的作用。 分子生物学的最新技术进步现在允许调查 创伤修复过程中胶原代谢的基因调控。 总mRNA将从真皮伤口成纤维细胞、从选择的成纤维细胞中分离。 在各种环境、营养、 和药理学条件，从体外纤维增生实验， 以及来自重组血凝块中的炎性细胞。 使用无细胞 蛋白质合成系统和cDNA探针分析， 转录或翻译控制可以在那些不同的细胞中确定。 系统. 这些多因素的炎症研究的最终结果， 伤口修复将是一个更好地了解胶原蛋白的步骤， 代谢是受调节的，可以用来更好地 控制异常愈合。

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.