Fibroblast growth factor 10 induces proliferation and differentiation of human primary cultured keratinocytes

Fibroblast growth factor 10 is a novel member of the fibroblast growth fact or family, which is involved in morphogenesis and epithelial proliferation. It is highly homologous to the keratinocyte growth factor (or fibroblast g rowth factor 7), a key mediator of keratinocyte growth and differentiation, Both fibroblast growth factor 10 and keratinocyte growth factor bind with high affinity to the tyrosine kinase keratinocyte growth factor receptor. H ere we analyzed the effect of fibroblast growth factor 10 on primary cultur es of human keratinocytes, grown in chemically defined medium, and we compa red the proliferative and differentiative cell responses to fibroblast grow th factor 10 with those induced by keratinocyte growth factor and epidermal growth factor. Cell counting, 5-bromo-2'-deoxyuridine incorporation, and w estern blot analysis showed that fibroblast growth factor 10, similarly to keratinocyte growth factor, not only is a potent mitogen for human keratino cytes, but also promotes the expression of both early differentiation marke rs K1 and K10 and late differentiation marker filaggrin in response to the Ca2+ signal, and seems to sustain the proliferative activity in suprabasal stratified cells, Immunoprecipitation/western blot analysis revealed that f ibroblast growth factor 10, similarly to keratinocyte growth factor, is abl e to induce tyrosine phosphorylation of keratinocyte growth factor receptor and of cellular substrates such as PLC gamma.