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 (FGF19) plays an important role in regulating cell proliferation. Psoriasis is characterized by the hyperproliferation of keratinocytes in skin lesions. However, whether FGF19 regulates the proliferation of keratinocytes in psoriasis remains unknown. In this study, we aimed to explore the potential relevance of FGF19 in psoriasis. We found that FGF19 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 FGF19 overexpression promoted the growth and proliferation of keratinocytes, while FGF19 knockdown showed opposite effect. Moreover, we found that FGF19 increased the phosphorylation of glycogen synthase kinase (GSK)-3β and promoted the expression of β-catenin and the activation of T cell factor 4 (TCF4) transcriptional activity. Notably, blocking Wnt/β-catenin signalling by silencing β-catenin partially reversed FGF19-mediated promotional effects on keratinocyte proliferation. In addition, FGFR4 inhibition significantly blocked the promotional effect of FGF19 on keratinocyte proliferation and GSK-3β/β-catenin/TCF4 signalling. Taken together, our results demonstrated that FGF19 contributes to sustaining the high proliferative ability of keratinocytes through promoting Wnt/GSK-3β/β-catenin signalling via FGFR4, highlighting the importance of FGF19 in the pathogenesis of psoriasis. Our study suggests that FGF19 may serve as a novel and potential therapeutic target for psoriasis.