EPIDERMAL GROWTH FACTOR STIMULATES WOUND HEALING IN VIVO

描述：(改编自申请人的摘要)生长控制 皮肤伤口愈合的机制是这一研究的中心焦点。 项目。既然在体内研究了各种外源生长因子 剃须显示了对一般伤口修复过程的生物影响，它 适时地剖析和定义细胞因子和 它们在离散的伤口愈合过程中的受体，如 角质形成细胞的增殖、迁移、炎性募集 种群和细胞外基质蛋白。EGF及EGF样蛋白 配体，它们的共同受体(EGF-r酪氨酸激酶)，以及随后 磷酸化基质将在独特的伤口愈合中进行研究 环境。表皮生长因子样配体及其受体的转录 (EGF-r)将通过原位杂交和Northern进行研究 印迹分析，蛋白质沉积将用 免疫组织化学染色，结合状态将研究 放射自显影。为了定义表皮损伤反应，EGF 信号级联将在迁移和增殖中进行比较 体外和体内创伤角质形成细胞的种群 表浅创伤模型(小鼠尾胶带剥离)。更深的伤口 环境(猪的切除伤口、人的烧伤、人类慢性 创伤)将被用来定义和对比细胞因子机制 它控制着细胞外基质蛋白。此外， 刺激性细胞因子与抑制性细胞因子之间的平衡 (TGFb超家族-BMP4)将使用BMP4转基因进行检测 小鼠创伤模型。最后，外源应用的分子与 EGF信令级联将作为实验工具用于 修饰伤口修复的表皮和/或间充质成分。

DESCRIPTION: (Adapted from the applicant's abstract) Growth control mechanisms in cutaneous wound healing are the central focus of this project. Now that in vivo studies with various exogenous growth factor shave shown a biological impact on general wound repair processes, it is timely to dissect and define signalling mechanisms of cytokines and their receptors on discrete wound healing processes such askeratinocyte proliferation, migration, recruitment of inflammatory populations and extracellular matrix proteins. EGF and EGF-like ligands, their common receptor (EGF-r tyrosinekinase), and subsequent phosphorylated substrates will be studied within unique wound healing environments. Transcription of EGF like ligands and their receptor (EGF-r) will be investigated using in situ hybridization and Northern blot analysis, protein deposition will be examined using immunohistochemical staining, and binding status will be studied with autoradiography. To define epidermal wounding responses, the EGF signalling cascade will be compared in migrating and proliferating populations of wound keratinocytes, both in vitro and in an in vivo model of superficial trauma (mouse tail tape stripping). Deeper wound environments (excisional porcine wounds, human burns, human chronic wounds) will be utilized to define and contrast cytokine mechanisms which control the extracellular matrix proteins. In addition, the balance between stimulatory cytokines(EGF) and inhibitory cytokines (TGFB superfamily-BMP4) will be examined using a BMP4 transgenic mouse wound model. Lastly, exogenously applied molecules relevant to the EGF signalling cascade will be used as experimental tools to modify epidermal and/or mesenchymal components of wound repair.