Organotypic Cocultures with Genetically Modified Mouse Fibroblasts as a Tool to Dissect Molecular Mechanisms Regulating Keratinocyte Growth and Differentiation
| Autor: | Marina Schorpp-Kistner, Axel Szabowski, Hans Jürgen Stark, Nicole Maas-Szabowski, Peter Angel, Andrea Kolbus, Sven Andrecht, Norbert E. Fusenig |
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| Rok vydání: | 2001 |
| Předmět: |
Adult
Keratinocytes Genetically modified mouse Proto-Oncogene Proteins c-jun JUNB Cellular differentiation Transgene Dermatology Biology skin equivalent Biochemistry Mice chemistry.chemical_compound Organ Culture Techniques medicine Animals Humans Skin equivalent human Molecular Biology mouse Mice Knockout Cell Differentiation Cell Biology Fibroblasts AP-1 Embryo Mammalian Cell biology medicine.anatomical_structure chemistry Knockout mouse Immunology Keratinocyte growth factor Keratinocyte Cell Division |
| Zdroj: | Journal of Investigative Dermatology. 116:816-820 |
| ISSN: | 0022-202X |
| DOI: | 10.1046/j.1523-1747.2001.01349.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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