c-Jun and JunB antagonistically control cytokine-regulated mesenchymal-epidermal interaction in skin.
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.
Szabowski
A
A
Division of Signal Transduction and Growth Control Deutsches Krebsforschungszentrum Im Neuenheimer Feld 280 69120, Heidelberg, Germany.
Maas-Szabowski
N
N
Andrecht
S
S
Kolbus
A
A
Schorpp-Kistner
M
M
Fusenig
N E
NE
Angel
P
P
D000818:Animals; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D004817:Epidermis / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008648:Mesoderm / Q000378:metabolism*; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D012867:Skin / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism
D016207:Cytokines; D004965:Estrogen Antagonists; C496453:FGF7 protein, human; C496454:Fgf7 protein, mouse; C496455:Fgf7 protein, rat; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D013629:Tamoxifen; D051523:Fibroblast Growth Factor 7; D005346:Fibroblast Growth Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003094:Collagen