Function of AP-1 target genes in mesenchymal-epithelial cross-talk in skin
Function of AP-1 target genes in mesenchymal-epithelial cross-talk in skin
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DOI：
10.1016/s0006-2952(02)01158-9
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发表时间：
2002-09-01
影响因子：
5.8
通讯作者：
Szabowski, A
中科院分区：
文献类型：
--
作者：
Angel, P;Szabowski, A
已经描述了越来越多的关于间充质-上皮相互作用在生理（例如胚胎发育）和病理（肿瘤发生）过程中的重要性的实例。这在皮肤中得到最好的说明，其中角质形成细胞增殖和分化的良好控制的平衡形成表皮的适当组织结构的基础。在这里，由表皮细胞（角质形成细胞）和下层真皮细胞（成纤维细胞）合成和分泌的细胞因子的双旁分泌环似乎起主要作用。这篇评论的目的是审查研究，已调查的转录因子AP-1（Jun/Fos）的特定亚基在这一调控网络中的作用。使用体外皮肤等效模型，通过调节成纤维细胞中白细胞介素-1（IL-1）诱导的角质形成细胞生长因子（KGF）和GM-CSF的表达，为c-Jun和JunB在皮肤中的间充质-上皮相互作用中的关键和特异性功能提供了强有力的证据。这些因素，反过来，调节角质形成细胞的增殖和分化之间的平衡，确保表皮的适当结构。这篇评论将总结我们目前对AP-1依赖性间充质-上皮相互作用的分子机制的了解，并讨论这些体外研究结果在皮肤生理学和病理学中的生理相关性。(C)2002年爱思唯尔科技有限公司All rights reserved.
An increasing number of examples on the importance of mesenchymal-epithelial interactions in physiological (e.g. embryonic development) and pathological (tumourigenesis) processes have been described. This is best illustrated in the skin, where the well-controlled balance of keratinocyte proliferation and differentiation forms the basis for a proper histoarchitecture of the epidermis. Here, a double paracrine loop of cytokines, which are synthesised and secreted by cells of the epidermis (keratinocytes) and the underlying dermis (fibroblasts) seems to play a major role. The aim of this commentary is to review research that has investigated the role of specific subunits of transcription factor AP-1 (Jun/Fos) in this regulatory network. Using an in vitro skin equivalent model strong evidence was provided for a critical and specific function of c-Jun and JunB in mesenchymal-epithelial interaction in the skin by regulating the expression of interleukin-1 (IL-1)-induced keratinocyte growth factor (KGF) and GM-CSF in fibroblasts. These factors, in turn, adjust the balance between proliferation and differentiation of keratinocytes ensuring proper architecture of the epidermis. This commentary will summarise our current knowledge on the molecular mechanisms underlying AP-1-dependent mesenchymal-epithelial interactions and discuss the physiological relevance of these in vitro findings in skin physiology and pathology. (C) 2002 Elsevier Science Inc. All rights reserved.