論文 - 詳細
| RRC ID | 50014 |
|---|---|
| 著者 | Chao HW, Doi M, Fustin JM, Chen H, Murase K, Maeda Y, Hayashi H, Tanaka R, Sugawa M, Mizukuchi N, Yamaguchi Y, Yasunaga JI, Matsuoka M, Sakai M, Matsumoto M, Hamada S, Okamura H. |
| タイトル | Circadian clock regulates hepatic polyploidy by modulating Mkp1-Erk1/2 signaling pathway. |
| ジャーナル | Nat Commun |
| Abstract |
Liver metabolism undergoes robust circadian oscillations in gene expression and enzymatic activity essential for liver homeostasis, but whether the circadian clock controls homeostatic self-renewal of hepatocytes is unknown. Here we show that hepatocyte polyploidization is markedly accelerated around the central vein, the site of permanent cell self-renewal, in mice deficient in circadian Period genes. In these mice, a massive accumulation of hyperpolyploid mononuclear and binuclear hepatocytes occurs due to impaired mitogen-activated protein kinase phosphatase 1 (Mkp1)-mediated circadian modulation of the extracellular signal-regulated kinase (Erk1/2) activity. Time-lapse imaging of hepatocytes suggests that the reduced activity of Erk1/2 in the midbody during cytokinesis results in abscission failure, leading to polyploidization. Manipulation of Mkp1 phosphatase activity is sufficient to change the ploidy level of hepatocytes. These data provide clear evidence that the Period genes not only orchestrate dynamic changes in metabolic activity, but also regulate homeostatic self-renewal of hepatocytes through Mkp1-Erk1/2 signaling pathway. |
| 巻・号 | 8(1) |
| ページ | 2238 |
| 公開日 | 2017-12-21 |
| DOI | 10.1038/s41467-017-02207-7 |
| PII | 10.1038/s41467-017-02207-7 |
| PMID | 29269828 |
| PMC | PMC5740157 |
| MeSH | Animals Circadian Clocks / genetics Dual Specificity Phosphatase 1 / metabolism* Hepatocytes / cytology Hepatocytes / metabolism* Hepatocytes / pathology Liver / cytology Liver / metabolism* Liver / pathology MAP Kinase Signaling System / physiology* Mice Mice, Knockout Microscopy Period Circadian Proteins / genetics* Polyploidy* Time-Lapse Imaging |
| IF | 12.121 |
| 引用数 | 8 |
| 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 | 21 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 遺伝子材料 | CSII-EF-MCS-IRES-hrGFP (RDB04382) |