SYNDECAN4 HEPARAN SULPHATE PROTEOGLYCAN IN CELL MIGRATION/CUTANEOUS WOUND REPAIR

为了解释毛细血管是如何形成的， 成纤维细胞和角质形成细胞对皮肤损伤反应的研究进展 重点已经放在细胞外基质和它的能力， 控制形态发生过程。 现在人们认识到，细胞是 能够整合来自化学和机械信号， 矩阵直接影响分化的表达， 生长特异性基因 细胞运动，作为一个重要组成部分， 内皮和间充质修复和再生过程，需要 细胞表面粘附受体之间的协调相互作用， 特异性细胞外基质（ECM）分子。 因此，我们认为， 鉴定调节细胞迁移过程的分子 对于开发新的靶向治疗非常重要， 加速受损的皮肤伤口愈合或增强修复过程 在高危伤口里 从根本上说，细胞周围的组成和浓度， 周围的基质成分对细胞速度有直接影响， 部分，通过控制细胞基质的粘合强度 通过单元格绑定图例的级别和可用性进行交互 粘附受体 通常，低细胞速度发生在配体上， 产生非常弱或非常强的能级f的密度 粘合强度 在这一框架内， 糖蛋白和蛋白聚糖的合成，以及它们的降解， 蛋白酶或其它因素将影响粘合剂配体的可用性。 然而，这些作用的介导需要配体与配体相互作用。 电池表面上的专用粘合剂接触， 协调负责细胞运动的环境信号。 在 除了含有整合素受体外，最近克隆的 跨膜硫酸肝素蛋白聚糖（HSPG），多配体蛋白聚糖-4，也 被定位在这些粘性复合物上。 具体目标1：确定syndecan-4在调节细胞凋亡中的作用 与底物配体密度相关的迁移及其对应性 从而影响整个电池/衬底的介电常数。 具体目标2：表征 多配体蛋白聚糖-4在迁移性角质形成细胞、真皮内皮细胞和 成纤维细胞，以及皮肤损伤模型。

To explain how capillaries form, as well as the organization of fibroblasts and keratinocytes in response to cutaneous injury, recent emphasis has been placed on the extracellular matrix and its ability to control morphogenic processes. It is now recognized that cells are capable of integrating both chemical and mechanical signals from the matrix which directly influences the expression of differentiation and growth specific genes. Cell locomotion, as an essential component of endothelial and mesenchymal repair and regenerative processes, requires the coordinated interaction between cell surface adhesion receptors and specific extracellular matrix (ECM) molecules. Therefore, identification of molecules which regulate the process of cell migration is important for the development of new targeted therapies for accelerating impaired dermal wound healing or enhancing repair processes in the high-risk wound. Fundamentally, the pericellular composition and concentration of surrounding matrix components has a direct effect on cell speed, in part, by controlling the adhesive strength of the cell-substrate interaction through the level and availability of bound legends for cell adhesion receptors. Typically, low cell speed occurs on ligand densities which yield either very weak or extremely strong levels f adhesive strength. Within this framework both the levels of specific glycoprotein and proteoglycan synthesis, as well as their degradation by proteases or other factors will influence adhesive ligand availability. However, mediation of these effects requires ligand interaction with specialized adhesive contacts on the cell surface which integrate and coordinate the environmental signals responsible for cell movement. In addition to containing integrin receptors, a recently cloned transmembrane heparin sulphate proteoglycan (HSPG), syndecan-4, has also been localized to these adhesive complexes. Specific Aim 1: Define the role of syndecan-4 in modulating cell migration in relation to substrate ligand density and its correspondence with effects on overall cell/substrate adhesiveness. Specific Aim 2: Characterize the spatiotemporal expression pattern of syndecan-4 in migrating keratinocytes, dermal endothelial cells, and fibroblasts, as well as in a model of cutaneous injury.