| First Author | Li F | Year | 2022 |
| Journal | Int J Biol Sci | Volume | 18 |
| Issue | 6 | Pages | 2597-2608 |
| PubMed ID | 35414779 | Mgi Jnum | J:324008 |
| Mgi Id | MGI:7262000 | Doi | 10.7150/ijbs.71719 |
| Citation | Li F, et al. (2022) BMAL1 regulates Propionibacterium acnes-induced skin inflammation via REV-ERBalpha in mice. Int J Biol Sci 18(6):2597-2608 |
| abstractText | 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-erbalpha, 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-kappaB/NLRP3 axis, which is known to be repressed by REV-ERBalpha (a direct target of BMAL1). Moreover, loss of Rev-erbalpha in mice exacerbated P. acnes-induced inflammation. In addition, Rev-erbalpha silencing attenuated the inhibitory effects of Bmal1 on P. acnes-induced inflammation. Bmal1 knockdown failed to modulate P. acnes-induced inflammation in Rev-erbalpha-silenced cells. It was thus proposed that Bmal1 restrained P. acnes-induced skin inflammation via its target REV-ERBalpha, which acts on the NF-kappaB/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. |
