UVB irradiation induces melanocyte damage through ferroptosis: mechanisms and implications

Ultraviolet B (UVB) irradiation can damage melanocytes, leading to skin disorders such as photoaging, melanoma, and vitiligo. While UVB-induced apoptosis and autophagy are well-studied, the role of ferroptosis, an iron-dependent form of programmed cell death, in melanocyte damage remains unclear.

Human epidermal melanocytes were exposed to UVB irradiation, and the effects on cell viability, apoptosis, reactive oxygen species (ROS) production, and iron metabolism were assessed using MTT, flow cytometry, DHE staining, and iron assays. RNA sequencing and bioinformatics analyses were conducted to explore differential gene expression and pathway activation. Ferrostatin-1 (Fer-1) was used to inhibit ferroptosis and evaluate its protective effects.

UVB exposure significantly reduced melanocyte viability, increased apoptosis, elevated ROS levels, and disrupted iron metabolism. Fer-1 treatment alleviated these effects by inhibiting ferroptosis. RNA sequencing showed activation of Ras, Rap1, PI3K-Akt, and Mitogen-Activated Protein Kinase (MAPK) signaling pathways, along with alterations in iron metabolism-related genes (e.g., FAXDC2, CYP3A5). Although classic ferroptosis core genes were not notably changed, the MAPK pathway and iron metabolism may indirectly contribute to UVB-induced ferroptosis.

UVB-induced melanocyte damage involves ferroptosis, potentially triggered by the MAPK pathway and iron metabolism. Fer-1 effectively protects melanocytes by inhibiting ferroptosis, underscoring its therapeutic potential for UVB-related skin disorders.