DEVELOPMENT OF AN IN VITRO WOUND HEALING MODEL

这项研究项目的长期目标是增加我们的 了解伤口收缩过程。更好地理解 收缩是寻求治疗策略的关键一步 对于收缩和结疤是必要的。为了实现这一目标，我们一直 研究伤口收缩体外模型的几个变种。 在接下来的五年里，我们计划采取一种综合的方法，在这种方法中，我们 将使用体外伤口收缩模型来研究细胞信号， 收缩和细胞凋亡的调节。具体目标#1侧重于 丝裂原活化蛋白激酶信号转导通路的激活 强调基质收缩、自分泌调节和即刻早期 基因转录。具体目标2侧重于负责的机制 为了刺激受压的和漂浮的胶原收缩，由血小板- 衍生生长因子和溶血磷脂酸在 调节漂浮和应激的基质收缩，以及 肌成纤维细胞分化中的机械应力。具体目标#3 重点关注导致细胞凋亡的因素 强调基质收缩。

The long term goal of this research project is to increase our understanding of the wound contraction process. A better understanding of contraction is an essential step in the search for therapeutic strategies necessary to contraction and scarring. Towards this goal, we have been studying several variations on an in vitro model of wound contraction. During the next five years, we plan an integrated approach in which we will use the in vitro wound contraction model to study cell signaling, regulation of contraction, and apoptosis. Specific Aim #1 focuses on the mitogen-activated protein kinase signal transduction pathways activated by stressed matrix contraction, autocrine regulation, and immediate early gene transcription. Specific Aim #2 focuses on the mechanisms responsible for stimulation of stressed and floating collagen contraction by platelet- derived growth factor and lysophosphatidic acid, differences in the regulation of floating and stressed matrix contraction, and the role of mechanical stress in myofibroblast differentiation. Specific Aim #3 focuses on the factors that contribute to apoptosis of cells undergoing stresses matrix contraction.