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BMAL1 regulates Propionibacterium acnes -induced skin inflammation via REV-ERBα in mice.
- Source :
-
International journal of biological sciences [Int J Biol Sci] 2022 Mar 21; Vol. 18 (6), pp. 2597-2608. Date of Electronic Publication: 2022 Mar 21 (Print Publication: 2022). - Publication Year :
- 2022
-
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.<br />Competing Interests: Competing Interests: The authors have declared that no competing interest exists.<br /> (© The author(s).)
- Subjects :
- ARNTL Transcription Factors genetics
ARNTL Transcription Factors metabolism
Animals
Inflammation genetics
Mice
NF-kappa B
NLR Family, Pyrin Domain-Containing 3 Protein metabolism
Propionibacterium acnes metabolism
Acne Vulgaris
Nuclear Receptor Subfamily 1, Group D, Member 1 genetics
Nuclear Receptor Subfamily 1, Group D, Member 1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1449-2288
- Volume :
- 18
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- International journal of biological sciences
- Publication Type :
- Academic Journal
- Accession number :
- 35414779
- Full Text :
- https://doi.org/10.7150/ijbs.71719