EPIDERMAL GROWTH FACTOR STIMULATES WOUND HEALING IN VIVO

描述：（改编自申请人摘要）生长控制 皮肤伤口愈合的机制是本发明的中心焦点， 项目 现在，在体内研究与各种外源性生长因子 剃须显示出对一般伤口修复过程的生物学影响， 及时剖析和定义细胞因子的信号传导机制， 它们的受体在离散的伤口愈合过程中， 角质形成细胞增殖、迁移、炎症募集 群体和细胞外基质蛋白。 EGF和EGF样 配体，它们的共同受体（EGF-r酪氨酸激酶），以及随后的 磷酸化底物将在独特的伤口愈合中进行研究 环境. EGF样配体及其受体的转录 （EGF-r）将使用原位杂交和北方 印迹分析，蛋白质沉积将使用 免疫组织化学染色，结合状态将研究与 放射自显影 表皮生长因子EGF 信号级联将比较迁移和增殖 伤口角质形成细胞群，在体外和体内 表浅创伤模型（小鼠尾带剥离）。 伤口更深 环境（切除的猪伤口、人烧伤、人慢性 伤口）将被用于定义和对比细胞因子机制 其控制细胞外基质蛋白。此外该 刺激性细胞因子（EGF）和抑制性细胞因子之间的平衡 (TGFB超家族-BMP 4）将使用BMP 4转基因 小鼠创伤模型。 最后，外源应用的分子与 EGF信号级联将被用作实验工具， 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.