REGULATION OF DIFFERENTIATION IN HUMAN EPITHELIAL CELLS

描述：（改编自申请人的摘要）这是一个 重新提交原先申请项目补助金，但现在 换了一个第一奖。 研究人员认为，归纳 相互作用对脊椎动物胚胎的正常发育至关重要。 的 交互可以包括物理模板的存在 细胞外基质蛋白，其可指导细胞迁移。 此外，对生长促进、生长抑制或 差异化因素可能起作用。 这些信号对于 正常组织结构的发育和维持 胚胎发生和成体损伤后的组织再生期间。 本研究中使用的组织模型是正常人新生儿皮肤。 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。 的 特定事件和调节因子介导真皮-表皮 相互作用目前尚不清楚。 研究中提出的问题 建议：（1）做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 基底膜成分（IV型胶原、VII型胶原或纤连蛋白）？ （二） TGF-β是否影响细胞类型特异性终末分化标志物， 人类角质细胞 例如，是转录的基因， 皮质被膜前体，外皮蛋白，通过TGF-β-1或 - β-2？ (3)基质附着的丧失是否会触发 角质细胞TGF-β？ (4)纤维连接蛋白或其他基底膜 成分诱导人角质形成细胞中外皮蛋白mRNA的表达？ (5)真皮成纤维细胞合成的细胞外基质是否暴露于 生长调节因子影响生长或分化 表皮角质形成细胞的特性？ 当前的目标是获得关于企业内容管理和 可扩散因子，如TGF-β，在正常人表皮中起作用， 分化 这些研究将产生基本信息， 将有助于理解和治疗发育引起的皮肤 畸形 此外，这些研究可能对战略很重要， 开发用于覆盖大伤口的最佳真皮等效物 地区 了解细胞外基质糖蛋白对 表皮角质形成细胞的分化特征将 促进皮肤等效物的配制。

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.