Bach2 regulates autophagy to modulate UVA induced photoaging in skin 1 fibroblasts

Mei Wang, Mingxing Lei, Li Chang, Yang Xing, Yingying Guo, Jingyi Chen, Jiefu Luo , Vega Widya Karisma, Muhammad Farrukh Nisar, Jörg W. Bartsch, Xia Lei, Julia Li Zhong

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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 38 autophay 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 41 demonstrated that Bach2 directly interacts with Beclin 1, Atg3, Atg7, and LC3 in 42 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.
Original languageEnglish
Pages (from-to)304-316
JournalFree Radical Biology and Medicine
Early online date18 Apr 2021
Publication statusPublished - 30 Jun 2021


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