Argatroban and Menadione exert protective effects in ultraviolet-irradiated skin inflammation: A transcriptomic analysis based on identification of iron overload related biomarkers

Abstract

Ultraviolet light (UV) can cause serious damage to human skin. The inflammatory reaction arising from repeated UV exposure leads to severe skin lesions and even promotes photo-carcinogenesis. Iron overload is featured by excessive iron intake and deposition and will promote inflammatory response inside cells. However, the core molecules involved in UV radiation induced iron overload and related anti-inflammatory strategies remain unclear. Signature genes involved in UV-irradiated skin were filtered through integrated datasets from the Gene Expression Omnibus (GEO) database. Subsequently, immune cell infiltration analysis was carried out to examine the relationship between signature gene expression and immune cell abundance. Single cell RNA-seq matrix data implicated in UV-irradiated skin was then applied to assess the expression level of signature genes in different cell clusters and to find out the core cell type and the key signaling pathway involved in UV radiation. Finally, cytological and animal experiments were conducted to investigate the potential of signature genes as therapeutic targets. SAT1 and RBMS1 were screened and validated as signature genes of UV irradiation. Immune cell infiltration analysis demonstrated that SAT1 and RBMS1 expression were associated closely with immune cell abundance, and skin fibroblasts were identified as the central cell type to communicate with other cell clusters in UV-irradiated skin. Disturbance of SAT1 exerted observably more suppressive effects on the release of inflammatory cytokines than overexpression of RBMS1. Two small molecule drugs targeting SAT1, namely Argatroban and Menadione, were predicted. Moreover, their therapeutic potentials in the treatment of UV-irradiated skin injury were confirmed experimentally.