Int J Biol Sci 2022; 18(6):2597-2608. doi:10.7150/ijbs.71719 This issue

Research Paper

BMAL1 regulates Propionibacterium acnes-induced skin inflammation via REV-ERBα in mice

Feng Li1#, Luomin Lin1#, Yiting He2, Guanghui Sun1, Dong Dong2✉, Baojian Wu3✉

1. College of pharmacy, Jinan University, Guangzhou 510632, China.
2. School of Medicine, Jinan University, Guangzhou, China.
3. Institute of Molecular Rhythm and Metabolism, Guangzhou University of Chinese Medicine, Guangzhou, China.
# These authors contributed equally to this work

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Citation:
Li F, Lin L, He Y, Sun G, Dong D, Wu B. BMAL1 regulates Propionibacterium acnes-induced skin inflammation via REV-ERBα in mice. Int J Biol Sci 2022; 18(6):2597-2608. doi:10.7150/ijbs.71719. Available from https://www.ijbs.com/v18p2597.htm

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Abstract

Graphic abstract

Acne vulgaris is a common skin disease, affecting over 80% of adolescents. Inflammation is known to play a central role in acne development. Here, we aimed to investigate the role of the central clock gene Bmal1 in acne-associated inflammation in mice. To this end, mice were injected intradermally with Propionibacterium acnes (P. acnes) to induce acne-associated skin inflammation. We found that Bmal1 and its target genes Rev-erbα, Dbp, Per1 and Cry2 were down-regulated in the skin of P. acnes-treated mice, suggesting a role of Bmal1 in the condition of acne. Supporting this, Bmal1-deleted or jet-lagged mice showed exacerbated P. acnes-induced inflammation in the skin. Regulation of P. acnes-induced inflammation by Bmal1 was further confirmed in RAW264.7 cells and primary mouse keratinocytes. Transcriptomic and protein expression analyses suggested that Bmal1 regulated P. acnes-induced inflammation via the NF-κB/NLRP3 axis, which is known to be repressed by REV-ERBα (a direct target of BMAL1). Moreover, loss of Rev-erbα in mice exacerbated P. acnes-induced inflammation. In addition, Rev-erbα silencing attenuated the inhibitory effects of Bmal1 on P. acnes-induced inflammation. Bmal1 knockdown failed to modulate P. acnes-induced inflammation in Rev-erbα-silenced cells. It was thus proposed that Bmal1 restrained P. acnes-induced skin inflammation via its target REV-ERBα, which acts on the NF-κB/NLRP3 axis to repress inflammation. In conclusion, Bmal1 disruption is identified as a potential pathological factor of acne-associated inflammation. The findings increase our understanding of the crosstalk between skin clock and acne and suggest targeting circadian rhythms as a promising approach for management of acne.

Keywords: Acne vulgaris, BMAL1, REV-ERBα, skin inflammation, circadian rhythms, P. acnes