FGF19 sustains the high proliferative ability of keratinocytes in psoriasis through the regulation of Wnt/GSK‐3β/β‐catenin signalling via FGFR4

Abstract Accumulating evidence has shown that fibroblast growth factor 19 ( FGF 19) plays an important role in regulating cell proliferation. Psoriasis is characterized by the hyperproliferation of keratinocytes in skin lesions. However, whether FGF 19 regulates the proliferation of keratinocytes in psoriasis remains unknown. In this study, we aimed to explore the potential relevance of FGF 19 in psoriasis. We found that FGF 19 was highly expressed in psoriatic skin from psoriasis patients, as well as keratinocytes that were stimulated with a cocktail of cytokines (M5), which is an in vitro model of psoriasis. Functional experiments demonstrated that FGF 19 overexpression promoted the growth and proliferation of keratinocytes, while FGF 19 knockdown showed opposite effect. Moreover, we found that FGF 19 increased the phosphorylation of glycogen synthase kinase ( GSK )‐3β and promoted the expression of β‐catenin and the activation of T cell factor 4 ( TCF 4) transcriptional activity. Notably, blocking Wnt/β‐catenin signalling by silencing β‐catenin partially reversed FGF 19‐mediated promotional effects on keratinocyte proliferation. In addition, FGFR 4 inhibition significantly blocked the promotional effect of FGF 19 on keratinocyte proliferation and GSK ‐3β/β‐catenin/ TCF 4 signalling. Taken together, our results demonstrated that FGF 19 contributes to sustaining the high proliferative ability of keratinocytes through promoting Wnt/ GSK ‐3β/β‐catenin signalling via FGFR 4, highlighting the importance of FGF 19 in the pathogenesis of psoriasis. Our study suggests that FGF 19 may serve as a novel and potential therapeutic target for psoriasis.