Fibroblast growth factors and skin diseases
Fibroblast growth factors (FGFs) are the key regulators of tissue development and repair. FGFs and their receptors (FGFRs) are also implicated in the pathogenesis of major human diseases including skin cancer and inflammatory diseases. A recent study demonstrated that the FGFR-associated signalling pathway has a tumour-suppressive function in the epidermis. Selective loss of FGFR1 and FGFR2 in mouse keratinocytes resulted in the development of chronic skin inflammation and cancer. The goal of the EU-funded FGFMIR (FGF-regulated miRNAs and their roles in skin inflammation and cancer) proposal was to unravel the mechanisms underlying the functions of FGFRs in the skin. The particular focus of the project was on the regulatory micro-RNAs (miRNAs). Small RNAs are emerging as key players in the regulation of signalling pathways in various tissues. However, FGF-regulated miRNAs in the skin were poorly characterised. Project researchers capitalised on the previously generated mouse models lacking FGFR1 and 2 in keratinocytes in the epidermis and in the hair follicles for their study of the mechanisms of FGF action in the skin. The animals develop a progressive inflammatory skin disease resembling atopic dermatitis (atopic eczema) in humans. Sequencing and the analysis of the RNA from the epidermis of FGFR-deficient and control mice identified a large number of novel FGF target genes. Some of the identified genes encode proteins and others encode FGF-regulated miRNAs. Functional analysis of these genes identified a previously unknown FGF-mediated signalling pathway in keratinocytes, which controls the susceptibility to skin diseases. The results of the project are of high medical relevance and researchers are evaluating the possibility of a patent application based on the findings.
Keywords
Fibroblast growth factor, skin cancer, inflammatory skin disease, FGFMIR, miRNA
