Abstract
Senescence is a cellular process that can be initiated by certain stressors such as UVA irradiation. The mechanism by which skin cells protect themselves from the UVA-induced senescence has not been fully investigated. Here, we demonstrate that Bach2 modulates the extent of UVA-induced photoaging through regulation of autophagy in skin fibroblasts. In fact chronic exposure of skin fibroblasts to UVA resulted in a significant decrease in Bach2 expression, both in vitro and in vivo. In addition, knockdown of Bach2 in skin fibroblasts led to an increased expression of cell senescence-related genes, which further enhanced the UVA irradiation-induced photoaging. On the other hand, the overexpression of Bach2 resulted in a decrease in the expression of cell senescence-related genes. We also demonstrate that the knockdown of Bach2 in skin fibroblasts can lead to a decreased expression of autophagy-related genes and vice versa, suggesting that autophagy is involved in Bach2-mediated regulation of senescence in skin fibroblasts. Additionally, inhibition of autophagy with autophagy inhibitor 3-MA suppressed the expression of autophagy-related proteins and promoted cell senescence. Furthermore, knockout of Atg5 or Atg7 in embryonic mouse fibroblasts led to a significant increase in the expression of cell senescence-related genes. Immunoprecipitation assays further demonstrated that Bach2 directly interacts with Beclin-1, Atg3, Atg7, and LC3 in fibroblasts. Taken together, these findings revealed a critical role for Bach2 in suppressing the UVA irradiation-induced cell senescence via autophagy in skin fibroblasts. Bach2 can therefore be a potential target for the therapy of UV-induced photoaging because of its ability to regulate the process of autophagy in the skin.