Possible treatment for UVB-induced skin injury: Anti-inflammatory and cytoprotective role of metformin in UVB-irradiated keratinocytes

Abstract

BackgroundExcessive inflammation and cell death induced by ultraviolet (UV) cause skin photodamage. Metformin possesses anti-inflammatory and cytoprotective effects. However, whether metformin inhibits inflammation and cell death in UVB-induced acute skin damage is unclear. ObjectiveTo evaluate the anti-inflammatory and cytoprotective effects of metformin in vitro and in vivo. Furthermore, its potential mechanism has been explored. MethodsTranscriptome sequencing and multiplex cytokines analysis were used to evaluate the validity of in vitro UVB-induced acute damage keratinocyte model and anti-inflammatory effects of metformin. We also determined the expression and nuclear translocation of CCAAT/enhancer-binding protein beta (C/EBPβ), an important transcriptional factor of Interleukin-1beta (IL-1β). Cell viability and cell death of keratinocytes were evaluated upon UVB irradiation in the presence or absence of metformin. 0.6% metformin cream was applied on UVB-irradiated mice to explore its pharmacological effects in vivo. ResultsTranscriptional landscape of 50 mJ/cm2 UVB-irradiated HaCaT cells is typical of UVB-induced acute damage keratinocyte model in vitro. Metformin alleviated transcription and secretion of IL-1β, Tumor Necrosis Factor-alpha, and Fibroblast Growth Factor 2, expression and nuclear translocation of C/EBPβ in this model. Metformin also protected keratinocytes from cell death caused by UVB-induced cellular secretions, which contributed to its cytoprotective effects. Topical administration of 0.6% metformin cream alleviated UVB-induced skin damage in mice. ConclusionWe proved the protective roles of metformin in UVB-challenged keratinocytes and UVB-irradiated mice, which indicated the potential value of metformin in topical therapy against skin photodamage.