Ultraviolet(UV)-induced DNA damage is a vital risk factor for the development of skin disorders including photoaging and cancers, which is primarily repaired by nucleotide excision repair (NER) pathway. Recent study has indicated that autophagy of keratinocytes can be enhanced following UV exposure. However, the implication of autophagy in UV-induced DNA damage is largely unknown. To address this, normal human fibrocytes (HFF) were disposed to UVA irradiation and their autophagy state was monitored by western blot and immunofluorescence. We confirmed that UVA exposure amplified the production of DNA damage, as well as autophagy in HFF. In addition, we demonstrated that activation of autophagy by rapamycin attenuated the production of DNA damage, whereas inhibition of autophagy by siRNA-ATG5 augmented it. Furthermore, we showed that DDB2, which plays critical role in the process of NER, changed its expression parallelly with autophagy alteration in HFF. Finally, Knockdown of Nrf2 prominently upregulated the production of DNA damage, as well as downregulated DDB2 expression in HFF with UVA exposure. These findings provide first evidence for the important role of autophagy in alleviating UVA-induced DNA damage in human fibrocytes through Nrf2-dependent NER pathway.

Autophagy Alleviates UVA-Induced DNA Damage in Fibrocyte by Activating the Nrf2-dependent Nucleotide Excision Repair Pathway