Eckert R L, Welter J F
Department of Physiology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-4970, USA.
Mol Biol Rep. 1996;23(1):59-70. doi: 10.1007/BF00357073.
The epidermis is a tissue that undergoes a very complex and tightly controlled differentiation program. The elaboration of this program is generally flawless, resulting in the production of an effective protective barrier for the organism. Many of the genes expressed during keratinocyte differentiation are expressed in a coordinate manner; this suggests that common regulatory models may emerge. The simplest model envisions a 'common regulatory element' that is possessed by all genes that are regulated together (e.g., involucrin and transglutaminase type 1). Studies to date, however, have not identified any such elements and, if anything, the available studies suggest that appropriate expression of each gene is achieved using sometime subtly and sometime grossly different mechanisms. Recent studies indicate that a variety of transcription factors (AP1, AP2, POU domain. Sp1, STAT factors) are expressed in the epidermis and, in many cases, multiple members of several families are present (e.g., AP1 and POU domain factors). The simultaneous expression of multiple members of a single transcription factor family provides numerous opportunities for complex regulation. Some studies suggest that specific members of these families interact with specific keratinocyte genes. The best studied of these families in epidermis is the AP1 family of factors. All of the known AP1 factors are expressed in epidermis [52] and each is expressed in a specific spatial pattern that suggests the potential to regulate multiple genes. It will be important to determine the role of each of these members in regulating keratinocyte gene expression. Finally, information is beginning to emerge regarding signal transduction in keratinocytes. Some of the early events in signal transduction have been identified (e.g., PLC and PKC activation, etc.) and some of the molecular targets of these pathways (e.g., AP1 transcription factors) are beginning to be identified. Eventually we can expect to elucidation of all of the steps between the interaction of the stimulating agent with its receptor and the activation of target gene expression.
表皮是一种经历非常复杂且受到严格调控的分化程序的组织。该程序的精细调控通常完美无缺，从而为机体构建出有效的保护屏障。许多在角质形成细胞分化过程中表达的基因是以协同方式表达的；这表明可能会出现共同的调控模式。最简单的模型设想存在一个“共同调控元件”，所有共同受调控的基因（如兜甲蛋白和1型转谷氨酰胺酶）都拥有该元件。然而，迄今为止的研究尚未发现任何此类元件，而且现有研究表明，每个基因的适当表达是通过有时微妙、有时显著不同的机制实现的。最近的研究表明，多种转录因子（AP1、AP2、POU结构域、Sp1、STAT因子）在表皮中表达，并且在许多情况下，几个家族的多个成员都存在（如AP1和POU结构域因子）。单个转录因子家族多个成员的同时表达为复杂调控提供了众多机会。一些研究表明，这些家族的特定成员与特定的角质形成细胞基因相互作用。在表皮中对这些家族研究得最深入的是AP1因子家族。所有已知的AP1因子都在表皮中表达[52]，并且每个因子都以特定的空间模式表达，这表明其具有调控多个基因的潜力。确定这些成员各自在调控角质形成细胞基因表达中的作用将非常重要。最后，关于角质形成细胞信号转导的信息也开始浮现。信号转导中的一些早期事件已被确定（如PLC和PKC激活等），并且这些途径的一些分子靶点（如AP1转录因子）也开始被识别。最终，我们有望阐明刺激剂与其受体相互作用与靶基因表达激活之间的所有步骤。
