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 了解伤口愈合过程。在接下来的四年里，我们 研究将集中在使用体外胶原基质进行伤口收缩方面 收缩模型。具体目标如下： (L)血小板衍化生长的机械调控机制分析 因子(PDGF)受体调节：将开展以下研究 确定PDGF受体的调节是否依赖于受体的减少 蛋白酪氨酸磷酸酶活性或蛋白酪氨酸磷酸酶活性升高。 (2)收缩调节的环状AMP信号通路分析： 将进行研究，以确定钙离子、蛋白激酶C和 胞浆磷脂酶A2在腺酰环化酶激活中的作用 应力松弛。 (3)利用胶原基质收缩分析瘢痕疙瘩成纤维细胞 模型：将进行研究，比较瘢痕疙瘩细胞生长和 机械应激与放松状态下细胞外基质的合成 胶原蛋白基质。 (4)成纤维细胞收缩调节机制分析。 将研究蛋白激酶对成纤维细胞收缩能力的调节 并在不同的力学条件下进行了比较。 (5)胞外小泡在细胞外基质中的作用分析 改建。成纤维细胞在应激过程中释放的基质小泡 松弛将被分析，以了解它们是否绑定或激活 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.