Fibroblast growth factor 10 protects against UVB‐induced skin injury by activating the ERK/YAP signalling pathway

Abstract

Objectives: Ultraviolet light B (UVB) irradiation can induce skin injury and result in keratinocytes proliferation inhibition. However, the molecular understanding of the repair during UVB-induced cell proliferation inhibition remains poorly understood.The purpose of this study was to explore the role and potential mechanism of FGF10 in promoting keratinocytes cell cycle and proliferation after UVB injury.Materials and Methods: Expression of FGF10 protein was analysed in skin treated with UVB radiation by immunohistochemistry. The proliferation potential was examined by Immunofluorescence, Western Blot and RT-PCR under UVB radiation, treated with FGF10 protein or overexpression of FGF10 using adeno-associated virus.CCK8 kit was used to further detect cell proliferation ability. Results:We found that FGF10 is highly expressed in skin treated with UVB. Overexpression of FGF10 has a protective effect against UVB-induced skin damage by balancing epidermal thickness and enhancing epidermal keratinocytes proliferation. Importantly, FGF10 is found to alleviate UVB-induced downregulation of YAP activity, then promoting keratinocytes proliferation. Disruption of YAP function, either with the small molecule YAP inhibitor Verteporfin (VP) or YAP small-interfering RNA (siRNA), largely abolishes the protective activity of FGF10 on epidermal keratinocytes proliferation. Meanwhile, disruption of ERK kinase (MEK) activity with U0126 or ERK siRNA hinder the positive influence of FGF10 on UVB-induced skin injury.Conclusion: FGF10 promotes epidermal keratinocytes proliferation during UVBinduced skin injury in an ERK/YAP-dependent manner. | INTRODUCTIONSkin is the largest organ in our body and primarily serves as a protective barrier against the external environment. 1,2 It can effectively prevent the invasion of harmful substances and pathogens, maintaining the stability of the internal environment. 3 UVB (280-320 nm) radiation, one of the most damaging solar UV emissions, can affect various skin structures, causing edema, erythema, hyperplasia, wrinkling, roughness, and premature aging, and can lead to the cell cycle and proliferation inihibition. 4,5 Studies have Nan Wang and Yetong Dong contributed equally to this work.