c-Jun and JunB antagonistically control cytokine-regulated mesenchymal-epidermal interaction in skin

Cell. 2000 Nov 22;103(5):745-55. doi: 10.1016/s0092-8674(00)00178-1.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Division
  • Cells, Cultured
  • Coculture Techniques
  • Collagen / metabolism
  • Cytokines / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Epidermis / metabolism*
  • Estrogen Antagonists / pharmacology
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors / metabolism
  • Fibroblasts / metabolism
  • Fluorescent Antibody Technique, Indirect
  • Granulocyte-Macrophage Colony-Stimulating Factor / antagonists & inhibitors
  • Granulocyte-Macrophage Colony-Stimulating Factor / metabolism
  • Humans
  • Keratinocytes / metabolism
  • Mesoderm / metabolism*
  • Mice
  • Models, Biological
  • Mutation
  • Proto-Oncogene Proteins c-jun / physiology*
  • RNA, Messenger / metabolism
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Skin / metabolism*
  • Tamoxifen / pharmacology
  • Transcription Factor AP-1 / metabolism

Substances

  • Cytokines
  • Estrogen Antagonists
  • FGF7 protein, human
  • Fgf7 protein, mouse
  • Fgf7 protein, rat
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Transcription Factor AP-1
  • Tamoxifen
  • Fibroblast Growth Factor 7
  • Fibroblast Growth Factors
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Collagen