Collagen I alleviates UVB-induced oxidative DNA damage and inhibits YAP-p73 apoptotic pathway in human keratinocytes...

Ultraviolet B (UVB) irradiation is closely associated with human skin damage. Collagen I is found to be protective against UVB-caused apoptosis in human keratinocytes HaCaT, and in this study, we further investigated the potential underlying mechanisms.

Oxidative DNA damage was evaluated by assessing the DNA damage marker γ-H2AX, 8-OHdG, and reactive oxygen species (ROS). Relative cell numbers were determined by MTT assays, while apoptosis was evaluated by Hoechst 33,342 and Annexin V/PI double staining. Western blotting and RT-PCR were used to examine protein and mRNA expressions, respectively. Immunofluorescence confocal microscopy was used to visualize targeted proteins.

Collagen I inhibits DNA damage and oxidative stress in HaCaT cells exposed to UVB irradiation. The YAP-p73 complex responds to DNA damages caused by UVB irradiation, and leads to the transcription of pro-apoptotic genes, including p21, PML and PUMA. DNA damage enhances ROS production, which further oxidatively damages DNA, forming a positive feedback loop. The protective effects of collagen I depend on the ROS restriction. Mitophagy, the process specifically eliminates the damaged mitochondria which are the main sources of cellular ROS, is restored by collagen I, and this contributes to the decreased ROS production, and the subsequent attenuation of cell apoptosis after UVB irradiation.

Collagen I-coating protects UVB-irradiated cells from YAP-p73 mediated apoptosis through restricting ROS production and thus alleviating DNA damages, owing to the restored mitophagy. Our study supports the clinical application of collagen products as anti-UVB agents.