Abstract
Interactions between mesenchymal and epithelial cells are responsible for organogenesis and tissue homeostasis. This mutual cross-talk involves cell surface proteins and soluble factors, which are mostly the result of regulated transcription. To elucidate dimer-specific functions of the AP-1 family of transcription factors, we reconstituted skin by combining primary human keratinocytes and mouse wild-type, c-jun(-/-), and junB(-/-) fibroblasts. We have discovered an antagonistic function of these AP-1 subunits in the fibroblast-mediated paracrine control of keratinocyte proliferation and differentiation, and traced this effect to the IL-1-dependent regulation of KGF and GM-CSF. These data suggest that the relative activation state of these AP-1 subunits in a non-cell-autonomous, transregulatory fashion directs regeneration of the epidermis and maintenance of tissue homeostasis in skin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation
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Cell Division
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Cells, Cultured
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Coculture Techniques
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Collagen / metabolism
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Cytokines / metabolism*
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Enzyme-Linked Immunosorbent Assay
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Epidermis / metabolism*
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Estrogen Antagonists / pharmacology
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Fibroblast Growth Factor 7
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Fibroblast Growth Factors / metabolism
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Fibroblasts / metabolism
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Fluorescent Antibody Technique, Indirect
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Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors
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Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
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Humans
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Keratinocytes / metabolism
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Mesoderm / metabolism*
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Mice
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Models, Biological
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Mutation
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Proto-Oncogene Proteins c-jun / physiology*
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RNA, Messenger / metabolism
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Rats
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Recombinant Fusion Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction
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Skin / metabolism*
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Tamoxifen / pharmacology
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Transcription Factor AP-1 / metabolism
Substances
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Cytokines
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Estrogen Antagonists
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FGF7 protein, human
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Fgf7 protein, mouse
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Fgf7 protein, rat
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Proto-Oncogene Proteins c-jun
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RNA, Messenger
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Recombinant Fusion Proteins
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Transcription Factor AP-1
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Tamoxifen
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Fibroblast Growth Factor 7
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Fibroblast Growth Factors
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Granulocyte-Macrophage Colony-Stimulating Factor
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Collagen