REGULATION OF DIFFERENTIATION IN HUMAN EPITHELIAL CELLS

描述：(改编自申请人的摘要)这是一份 重新提交原先申请项目拨款但现在 改成了一等奖。调查员认为，归纳性 相互作用对脊椎动物胚胎的正常发育至关重要。这个 交互可能包括物理模板的存在，例如 可能指导细胞迁移的细胞外基质蛋白。 此外，对促进生长、抑制生长或 差异化因素可能起到一定作用。这些信号对于 正常组织结构的发育和维持 成体胚胎发生和损伤后组织再生过程。 本研究使用的组织模型为正常新生儿皮肤。 正常皮肤发育中的许多事件依赖于 表皮角质形成细胞和真皮细胞类型之间的信息。这个 调节真皮-表皮的特定事件和调节因子 相互作用目前尚不清楚。研究中提出的问题 建议有：(1)DO对人角质形成细胞的生长刺激因子 (表皮生长因子和角质形成细胞生长因子)或生长 抑制因子(转化生长因子-β)影响细胞合成 基底膜成分(IV型、VI型胶原或纤维连接蛋白)？(2) 转化生长因子-β是否影响细胞类型特异的终末分化标志物 人类角质形成细胞？例如，基因的转录是一种 角化包膜前体，总蛋白，经转化生长因子-β-1或 -β-2？(3)底物附着的丧失是否会触发 角质形成细胞转化生长因子-β？(4)纤维连接蛋白或其他基底膜 组份诱导人角质形成细胞中总蛋白的表达？ (5)真皮成纤维细胞合成的细胞外基质是否暴露 以生长调节因素影响生长或分化 表皮角质形成细胞的特性？ 眼下的目标是获得有关ECM和 扩散因子，如转化生长因子-β，在正常人表皮中发挥作用 差异化。这些研究将产生基本信息， 将有助于理解和治疗由发育引起的皮肤 畸形。此外，这些研究可能对战略具有重要意义。 开发覆盖大面积创面的最佳真皮替代物 区域。细胞外基质糖蛋白对血管内皮生长因子影响的研究进展 表皮角质形成细胞的分化特征 促进真皮等效物的配制。

DESCRIPTION: (Adapted from the applicant's abstract) This is a re-submission of an application originally for a project grant but now changed to one for a FIRST Award. The investigator suggests that inductive interactions are critical to normal development in vertebrate embryos. The interactions may include the presence of physical templates such as extracellular matrix proteins which may direct cell migration. Additionally, elaboration of growth-promoting, growth-inhibiting, or differentiating factors may play a role. These signals are important for the development and maintenance of normal tissue architecture during embryogenesis and during tissue regeneration following injury in the adult. The tissue model utilized in this research is normal human neonatal skin. Many events in normal skin development rely upon the exchange of information between epidermal keratinocytes and dermal cell types. The specific events and regulatory factors that mediate dermal-epidermal interactions are currently unknown. Questions addressed in the research proposal are: (1) Do growth stimulatory factors for human keratinocytes (epidermal growth factor and keratinocyte growth factor) or growth inhibitory factors (transforming growth factor-betas) affect synthesis of basement membrane components (collagen types IV, VII, or fibronectin)? (2) Do TGF-betas affect cell type-specific terminal differentiation markers in human keratinocytes? For example, is transcription of the gene for a cornified envelope precursor, involucrin, enhanced by TGF-beta-1 or -beta-2? (3) Does loss of substratum attachment trigger expression of keratinocyte TGF-betas? (4) Can fibronectin or other basement membrane components induce expression of involucrin mRNA in human keratinocytes? (5) Do the extracellular matrices synthesized by dermal fibroblasts exposed to growth regulatory factors affect the growth or differentiation properties of epidermal keratinocytes? The immediate goal is to gain information on the role that ECM and diffusible factors, such as TGF-betas, play in normal human epidermal differentiation. These studies will generate fundamental information that will aid in understanding and treatment of developmentally caused skin malformations. In addition, these studies may be important for strategies to develop optimal dermal equivalents for the coverage of large wound areas. Knowledge of the effects of extracellular matrix glycoproteins on the differentiation characteristics of epidermal keratinocytes will facilitate the formulation of dermal equivalents.