COLLAGEN METABOLISM IN WOUND REPAIR AND KELOID

这个项目的长期目标是阐明细胞 相互作用及参与调控的分子机制 伤口修复过程中的胶原蛋白代谢。首先要达到目标 通过确定是否存在一组专门化的亚群 创伤后的成纤维细胞，每个细胞都有不同的产生潜力 胶原蛋白。这些研究可以解释为什么某些个体 容易过度形成疤痕(瘢痕疙瘩和增生性瘢痕)， 而其他人则伤口愈合能力下降(疝气和营养不良)。其他 研究主要集中在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植入动物和人类体内以鉴定炎性细胞 正常伤口中与结缔组织沉积有关的动力学 治疗和遵循药物调节。此外，有可能 炎症细胞在最初的伤口基质中产生胶原将 利用光和电子免疫组织化学进行进一步的探索， 生化分析和分子探针分析。一种体外实验动物模型的建立 纤维增生症将用于重建伤口环境，以进一步 确定炎症、细胞和体液参与者在 终极纤维化反应。一种来自巨噬细胞的低分子物质 我们分离的成纤维细胞的趋化因子将被提纯 进一步确定其在成纤维细胞趋化中的作用。 分子生物学的最新技术进步现在使研究成为可能 伤口修复过程中胶原蛋白代谢的遗传调控。 总mRNA将从真皮伤口成纤维细胞中分离，从选定的 在不同环境、营养条件下培养的成纤维细胞亚群 和药物条件，从体外成纤维实验， 以及重组血液凝块中的炎性细胞。使用无手机 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这些不同的 系统。这些多因素研究的最终结果是炎症和 伤口修复将更好地理解胶原蛋白 新陈代谢是调节的和特定的机制，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.