Organotypic cocultures with genetically modified mouse fibroblasts as a tool to dissect molecular mechanisms regulating keratinocyte growth and differentiation
Organotypic cocultures with genetically modified mouse fibroblasts as a tool to dissect molecular mechanisms regulating keratinocyte growth and differentiation
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DOI：
10.1046/j.1523-1747.2001.01349.x
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发表时间：
2001-05-01
影响因子：
6.5
通讯作者：
Fusenig, NE
中科院分区：
文献类型：
--
作者：
Maas-Szabowski, N;Szabowski, A;Fusenig, NE
角质形成细胞和成纤维细胞的器官型共培养会产生正常的表皮，无论成纤维细胞的物种和组织来源如何。使用小鼠成纤维细胞和人角质形成细胞有助于鉴定参与表皮组织重建和生长调节的化合物的来源。此外，来自转基因或敲除小鼠的遗传修饰的成纤维细胞的角质形成细胞表型的功能意义，甚至那些表现出胚胎致死表型的，可以在这样的异源体外组织等同物中进行研究。在这里，我们传达了此类研究的结果，揭示了AP-1成分c-Jun和JunB缺陷的小鼠成纤维细胞分别对人类角质形成细胞生长和分化的拮抗功能。此外，造血生长因子粒细胞巨噬细胞集落刺激因子已被鉴定为角质形成细胞生长和分化的新调节剂。如将在别处详细报道的，粒细胞巨噬细胞集落刺激因子和角质形成细胞生长因子都已被鉴定为成纤维细胞-角质形成细胞相互作用的主要介质，并且它们的表达通过AP-1由上皮细胞释放的白细胞介素-1诱导，因此，这些异源共培养物提供了一种新的有希望的工具，用于阐明上皮细胞-间充质相互作用及其对上皮细胞增殖和分化的影响。
Organotypic cocultures of keratinocytes and fibroblasts generate a normal epidermis irrespective of the species and tissue origin of fibroblasts. The use of mouse fibroblasts and human keratinocytes facilitates the identification of the origin of compounds involved in epidermal tissue reconstitution and growth regulation. Moreover, the functional significance for the keratinocyte phenotype of genetically modified fibroblasts from transgenic or knockout mice, even those exhibiting an embryonic lethal phenotype, can be studied in such heterologous in vitro tissue equivalents. Here we communicate results of such studies revealing the antagonistic function of mouse fibroblasts defective in the AP-1 constituents c-Jun and JunB, respectively, on human keratinocyte growth and differentiation. Furthermore, the hematopoietic growth factor granulocyte macrophage-colony stimulating factor has been identified as a novel regulator of keratinocyte growth and differentiation. As will be reported in detail elsewhere both granulocyte macrophage-colony stimulating factor and keratinocyte growth factor have been identified as major mediators of fibroblast-keratinocyte interactions and their expression is induced via AP-1 by interleukin-1 released by the epithelial cells, Thus, these heterologous cocultures provide a novel promising tool for elucidating molecular mechanisms of epithelial-mesenchymal interactions and their consequences on epithelial cell proliferation and differentiation.