Abstract
Fibroblast growth factors (FGFs) play key roles in the development of different tissues and organs, including the skin. However, there is little information on the potential roles of FGFs in the pathogenesis of human skin diseases. We recently demonstrated that FGFR signaling in keratinocytes is important for the prevention of skin inflammation. Thus, mice lacking FGF receptors 1 and 2 in keratinocytes develop a chronic inflammatory skin disease, which strongly resembles Atopic Dermatitis in humans. Using a combination of mouse genetics, transcriptomics and proteomics we identified the cellular and molecular mechanisms underlying the development of inflammatory skin disease in our mouse model and we demonstrate the potential relevance of these findings for Atopic Dermatitis in humans. In addition, we unravelled essential functions of FGFs in repair of skin and liver. These activities result from the FGF-mediated regulation of genes involved in survival, proliferation and migration of keratinocytes and hepatocytes. Taken together, our work identified important roles of FGFs in homeostasis and repair of epithelial tissues and suggest modulation of FGF signaling as a potent strategy for the improvement of tissue regeneration and prevention of inflammatory disease.
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