Final Report Summary - FGFMIR (FGF-regulated miRNAs and their roles in skin inflammation and cancer)
Novel activities of Fibroblast Growth Factors in skin homeostasis and disease
Fibroblast growth factors (FGFs) are master regulators of development and tissue repair, and they are involved in the pathogenesis of several major human diseases, including inflammatory diseases. To study the mechanisms of FGF action in the skin we previously generated mice lacking FGF receptors 1 and 2 in keratinocytes of the uppermost layer of the skin, the epidermis, and in the hair follicles. These mice develop a progressive inflammatory skin disease with features resembling the severe inflammatory skin disease Atopic Dermatitis (Atopic Eczema) in humans. The phenotype only develops approximately 3 weeks after birth and therefore, young mice are ideally suited to identify and characterize the direct targets of FGF signaling in the epidermis in vivo. Upon sequencing of the RNA from the isolated epidermis of FGFR-deficient and control mice prior to the development of the phenotype we identified a large number of novel FGF target genes, of which some encode proteins and others encode non-coding ribonucleic acids. Functional analysis of a subset of these genes identified a previously unidentified FGF-mediated signaling pathway in keratinocytes, which controls the susceptibility to important skin diseases. Our findings are of high medical relevance, and we are evaluating the possibility of filing a patent application based on our findings. Additionally, a manuscript describing these findings is currently in preparation, and we expect to submit it later this year. The training of the research fellow funded by the Marie Curie fellowship was highly successful, and he was recently been invited to a Gordon Research Conference as a plenary speaker. Most importantly, he has now all the skills required for an independent scientific position.
Fibroblast growth factors (FGFs) are master regulators of development and tissue repair, and they are involved in the pathogenesis of several major human diseases, including inflammatory diseases. To study the mechanisms of FGF action in the skin we previously generated mice lacking FGF receptors 1 and 2 in keratinocytes of the uppermost layer of the skin, the epidermis, and in the hair follicles. These mice develop a progressive inflammatory skin disease with features resembling the severe inflammatory skin disease Atopic Dermatitis (Atopic Eczema) in humans. The phenotype only develops approximately 3 weeks after birth and therefore, young mice are ideally suited to identify and characterize the direct targets of FGF signaling in the epidermis in vivo. Upon sequencing of the RNA from the isolated epidermis of FGFR-deficient and control mice prior to the development of the phenotype we identified a large number of novel FGF target genes, of which some encode proteins and others encode non-coding ribonucleic acids. Functional analysis of a subset of these genes identified a previously unidentified FGF-mediated signaling pathway in keratinocytes, which controls the susceptibility to important skin diseases. Our findings are of high medical relevance, and we are evaluating the possibility of filing a patent application based on our findings. Additionally, a manuscript describing these findings is currently in preparation, and we expect to submit it later this year. The training of the research fellow funded by the Marie Curie fellowship was highly successful, and he was recently been invited to a Gordon Research Conference as a plenary speaker. Most importantly, he has now all the skills required for an independent scientific position.