DEVELOPMENT OF AN IN VITRO WOUND HEALING MODEL

该研究项目的长期目标是提高我们的 了解伤口愈合过程。在接下来的四年里，我们 研究将集中于使用体外胶原基质的伤口收缩 收缩模型 具体目标如下： (l)血小板源性生长的机械调节机制分析 因子（PDGF）受体调节：将进行研究， 确定PDGF受体的调节是否依赖于受体减少 激酶活性或增加的蛋白酪氨酸磷酸酶活性。 (2)收缩调节的环AMP信号传导途径的分析： 将进行研究，以确定Ca2+，PKC， 腺苷酸环化酶激活中的胞质磷脂酶A2 应力松弛 (3)瘢痕疙瘩成纤维细胞胶原基质收缩分析 模型：将进行研究以比较瘢痕疙瘩细胞生长和 细胞外基质合成在机械应力与放松 胶原基质。 (4)成纤维细胞收缩性的调控机制分析。 将研究蛋白激酶对成纤维细胞收缩力的调节 并在不同的机械条件下进行比较。 (5)细胞外囊泡在细胞外基质中的作用分析 重塑 成纤维细胞在应激过程中释放的基质囊泡 放松将被分析，以了解它们是否结合或激活 金属蛋白酶参与基质重塑。

The long term goal of this research project is to increase our understanding of the wound healing process. Over the next four years, our studies will focus on wound contraction using in vitro collagen matrix contraction models. Specific aims are as follows: (l) Analysis of the mechanoregulated mechanism of platelet derived growth factor (PDGF) receptor modulation: Studies will be carried out to determine if modulation of PDGF receptors depends on decreased receptor kinase activity or on increased protein tyrosine phosphatase activity. (2) Analysis of the contraction regulated cyclic AMP signaling pathway: Studies will be carried out to determine the roles of Ca2+, PKC, and cytoplasmic phospholipase A2 in adenylyl cyclase activation following stress relaxation. (3) Analysis of keloid fibroblasts using the collagen matrix contraction model: Studies will be carried out to compare keloid cell growth and extracellular matrix synthesis in mechanically stressed vs. relaxed collagen matrices. (4) Analysis of regulatory mechanisms for fibroblast contractility. Regulation of fibroblast contractility by protein kinases will be studied and compared under different mechanical conditions. (5) Analysis of the role of ectocytotic vesicles in extracellular matrix remodeling. Matrix vesicles released by fibroblasts during stress relaxation will be analyzed to learn if they bind or activate metalloproteinases involved in matrix remodeling.