Abstract

Deep mining of the molecular mechanisms underlying skin aging is critical for the development of novel therapeutic targets. The aim of this study was to explore potential key signatures and underlying mechanisms in skin aging. Bioinformatics tools were used to evaluate the differentially expressed genes (DEGs), perform enrichment analysis, and construct protein-protein interaction networks on datasets. The hub genes were identified using Cytoscape software and then confirmed by qRT-PCR and Western Blot in vitro. We focused on the possible roles of GRWD1. GRWD1 expression were suppressed in senescence model of HDF. After GRWD1 overexpression by lentivirus in primary human dermal Fibroblasts (HDF), transcriptome sequencing (RNA-seq) was performed. GRWD1 has influence on the inflammation and immune responses. IFN signaling pathway genes significant increase in senescence HDF. When GRWD1 overexpressed, decreased expression of IFN pathway is validated. Besides, age-related markers p16, IL-6, and IL-8 expression decreased and Lamin B expression also increased. It was also proved after GRWD1 knockdown. GRWD1 was identified as a novel signature in skin aging. GRWD1 directly interact with IRF3. GRWD1 overexpression can down regulate IFN signaling pathway key genes expression, further diminish IFN aging-inducing effects. GRWD1 alleviates skin inflammatory responses by suppressing IRF3-mediated IFN pathway activation. Our findings suggest that GRWD1 may serve as a molecular biomarker and further as a potential therapeutic target for skin aging. Summary Identification of GRWD1 as a novel signature in skin aging. GRWD1 alleviates skin aging by suppressing IRF3-mediated IFN signaling. GRWD1 has anti-aging and anti-inflammatory effects. GRWD1 may serve as a molecular biomarker and a promising therapeutic target for skin aging.