Fibroblast growth factor receptors 1 and 2 in keratinocytes control the epidermal barrier and cutaneous homeostasis

Fibroblast growth factors (FGFs) are master regulators of organogenesis and tissue homeostasis. In this study, we used different combinations of FGF receptor (FGFR)-deficient mice to unravel their functions in the skin. Loss of the IIIb splice variants of FGFR1 and FGFR2 in keratinocytes caused prog...

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Bibliographic Details
Published in:The Journal of cell biology 2010-03, Vol.188 (6), p.935-952
Main Authors: Yang, Jingxuan, Meyer, Michael, Müller, Anna-Katharina, Böhm, Friederike, Grose, Richard, Dauwalder, Tina, Verrey, Francois, Kopf, Manfred, Partanen, Juha, Bloch, Wilhelm, Ornitz, David M, Werner, Sabine
Format: Article
Language:English
Subjects:
Alleles
Animals
Antibodies
Biochemistry
Cell growth
Cells
Cells, Cultured
Cytokines
Dermis
Epidermis
Epidermis - cytology
Epidermis - metabolism
Homeostasis
Keratinocytes
Keratinocytes - cytology
Keratinocytes - metabolism
Mast cells
Mice
Mice, Inbred C57BL
Mice, Transgenic
Proteins
Receptor, Fibroblast Growth Factor, Type 1 - genetics
Receptor, Fibroblast Growth Factor, Type 1 - metabolism
Receptor, Fibroblast Growth Factor, Type 2 - genetics
Receptor, Fibroblast Growth Factor, Type 2 - metabolism
Receptors
Reverse Transcriptase Polymerase Chain Reaction
Skin
T lymphocytes
Tight junctions
Tissues
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Summary:Fibroblast growth factors (FGFs) are master regulators of organogenesis and tissue homeostasis. In this study, we used different combinations of FGF receptor (FGFR)-deficient mice to unravel their functions in the skin. Loss of the IIIb splice variants of FGFR1 and FGFR2 in keratinocytes caused progressive loss of skin appendages, cutaneous inflammation, keratinocyte hyperproliferation, and acanthosis. We identified loss of FGF-induced expression of tight junction components with subsequent deficits in epidermal barrier function as the mechanism underlying the progressive inflammatory skin disease. The defective barrier causes activation of keratinocytes and epidermal γδ T cells, which produce interleukin-1 family member 8 and S100A8/A9 proteins. These cytokines initiate an inflammatory response and induce a double paracrine loop through production of keratinocyte mitogens by dermal cells. Our results identify essential roles for FGFs in the regulation of the epidermal barrier and in the prevention of cutaneous inflammation, and highlight the importance of stromal-epithelial interactions in skin homeostasis and disease.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.200910126