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

doi:10.1016/j.freeradbiomed.2021.04.003

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

Research output: Contribution to journal › Article › peer-review

16 Citations (SciVal)

168 Downloads (Pure)

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 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 language	English
Pages (from-to)	304-316
Journal	Free Radical Biology and Medicine
Volume	169
Early online date	18 Apr 2021
DOIs	https://doi.org/10.1016/j.freeradbiomed.2021.04.003
Publication status	Published - 30 Jun 2021

Funding

This work was supported by the National Natural Science Foundation of China ( 81573073 , 82003384 , 81573071 , and 81773348 ), the Fundamental Research Funds for the Central Universities (2020CDJYGSG001 and 2020CDJYGSG003), Chongqing Talents Program (CQYC2020058022), Scientific Research Foundation from Chongqing University ( 02210011044110 ), and the 111 Project of Biomechanics and Tissue Repair (B605). This work was also supported by Series of Evidence-Based Study on Hot Spring Wellness, Chongqing Municipal Commission of Culture and Tourism Development (to JL Zhong), and the Initial Research Funds for the Ph.D in Zunyi Medical University ( 2018-5772-072 ), 2020 City-School Joint Project, Science and Technology Plan Project (2018-5772-066) of Guizhou Province ( 2021-565 ) (to Mei Wang), and a Biotechnology and Biological Sciences Research Council (BBSRC, Grant no BB/J005223/1 ), UK (to C.Pourzand). The authors thank Professor Ji Li (Central South University) and Professor Xianjun Qu (Capital Medical University) for useful discussions. This work was supported by the National Natural Science Foundation of China (81573073, 82003384, 81573071, and 81773348), the Fundamental Research Funds for the Central Universities (2020CDJYGSG001 and 2020CDJYGSG003), Chongqing Talents Program (CQYC2020058022), Scientific Research Foundation from Chongqing University (02210011044110), and the 111 Project of Biomechanics and Tissue Repair (B605). This work was also supported by Series of Evidence-Based Study on Hot Spring Wellness, Chongqing Municipal Commission of Culture and Tourism Development (to JL Zhong), and the Initial Research Funds for the Ph.D in Zunyi Medical University (2018-5772-072), 2020 City-School Joint Project, Science and Technology Plan Project (2018-5772-066) of Guizhou Province (2021-565) (to Mei Wang), and a Biotechnology and Biological Sciences Research Council (BBSRC, Grant no BB/J005223/1), UK (to C.Pourzand). The authors thank Professor Ji Li (Central South University) and Professor Xianjun Qu (Capital Medical University) for useful discussions.

Access to Document

10.1016/j.freeradbiomed.2021.04.003

Manuscript 03.16. 2021 unmarked.PDFAccepted author manuscript, 486 KBLicence: CC BY-NC-ND

1 Finished

Mitochondrial and Lysosomal-Targeted Iron Chelators for the Monitoring and Adjustment of Cellular Labile Iron Pools
Pourzand, C. (PI)
Biotechnology and Biological Sciences Research Council
3/04/12 → 2/04/15
Project: Research council

Cite this

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 2021, 'Bach2 regulates autophagy to modulate UVA induced photoaging in skin 1 fibroblasts', Free Radical Biology and Medicine, vol. 169, pp. 304-316. https://doi.org/10.1016/j.freeradbiomed.2021.04.003

@article{c171f6ac23744fcda6157da793d90625,

title = "Bach2 regulates autophagy to modulate UVA induced photoaging in skin 1 fibroblasts",

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 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.",

author = "{Mei Wang} and {Mingxing Lei} and {Li Chang} and {Yang Xing} and {Yingying Guo} and {Jingyi Chen} and Charareh Pourzand and {Jiefu Luo} and {Vega Widya Karisma} and {Muhammad Farrukh Nisar} and {J{\"o}rg W. Bartsch} and {Xia Lei} and {Julia Li Zhong}",

year = "2021",

month = jun,

day = "30",

doi = "10.1016/j.freeradbiomed.2021.04.003",

language = "English",

volume = "169",

pages = "304--316",

journal = "Free Radical Biology and Medicine",

issn = "0891-5849",

publisher = "Elsevier",

}

TY - JOUR

T1 - Bach2 regulates autophagy to modulate UVA induced photoaging in skin 1 fibroblasts

AU - Mei Wang

AU - Mingxing Lei

AU - Li Chang

AU - Yang Xing

AU - Yingying Guo

AU - Jingyi Chen

AU - Pourzand, Charareh

AU - Jiefu Luo

AU - Vega Widya Karisma

AU - Muhammad Farrukh Nisar

AU - Jörg W. Bartsch

AU - Xia Lei

AU - Julia Li Zhong

PY - 2021/6/30

Y1 - 2021/6/30

N2 - 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.

AB - 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.

U2 - 10.1016/j.freeradbiomed.2021.04.003

DO - 10.1016/j.freeradbiomed.2021.04.003

M3 - Article

SN - 0891-5849

VL - 169

SP - 304

EP - 316

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -

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

Abstract

Funding

Access to Document

Fingerprint

Projects

Mitochondrial and Lysosomal-Targeted Iron Chelators for the Monitoring and Adjustment of Cellular Labile Iron Pools

Cite this