論文 - 詳細
| RRC ID | 89284 |
|---|---|
| 著者 | Tsuruta A, Hirao N, Shibata M, Yoshida Y, Izumi Y, Shindo N, Shiiba Y, Higashi K, Inoki T, Kai Y, Hiraoka Y, Yamauchi T, Ojida A, Bamba T, Matsunaga N, Koyanagi S, Ohdo S. |
| タイトル | The circadian clock component BMAL1 enhances macrophage inflammation by nuclear translocation of peroxisomal β-oxidation enzyme MFP2. |
| ジャーナル | Cell Rep |
| Abstract |
The circadian clock regulates diverse immune functions, yet the role of clock components in macrophage inflammation remains controversial, with both pro- and anti-inflammatory effects reported. Here, we identify a previously unrecognized mechanism by which the core circadian clock component BMAL1 enhances the inflammatory response of macrophages through the nuclear translocation of the peroxisomal β-oxidation enzyme multi-functional protein 2 (MFP2). BMAL1 drives MFP2 accumulation in the nucleus, where MFP2 contributes to acetyl-CoA production and acetylation of the NF-κB subunit p65, thereby facilitating M1 polarization and inflammatory chemokine expression. Nuclear MFP2 levels oscillate in a diurnal manner in the liver, but this rhythmicity is abolished in Bmal1-deficient mice. Macrophage-specific deletion of BMAL1 alleviates diethylnitrosamine-induced hepatic inflammation and tumorigenesis, concomitant with reduced inflammatory gene expression. These findings uncover a BMAL1-dependent nuclear metabolic pathway that links circadian regulation of macrophage inflammation and suggest that targeting nuclear MFP2 may offer a therapeutic approach for inflammatory diseases and tumorigenesis. |
| 巻・号 | 45(6) |
| ページ | 117480 |
| 公開日 | 2026-6-9 |
| DOI | 10.1016/j.celrep.2026.117480 |
| PII | S2211-1247(26)00558-9 |
| PMID | 42268717 |
| IF | 8.109 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 30 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 66.2 |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) NIH3T3-3(RCB0150) |