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Title: Circadian clock regulates hepatic polyploidy by modulating Mkp1-Erk1/2 signaling pathway
Authors: Chao, Hsu-Wen
Doi, Masao  kyouindb  KAKEN_id  orcid (unconfirmed)
Fustin, Jean-Michel  kyouindb  KAKEN_id  orcid (unconfirmed)
Chen, Huatao
Murase, Kimihiko
Maeda, Yuki
Hayashi, Hida
Tanaka, Rina
Sugawa, Maho
Mizukuchi, Naoki
Yamaguchi, Yoshiaki  kyouindb  KAKEN_id  orcid (unconfirmed)
Yasunaga, Jun-ichirou
Matsuoka, Masao
Sakai, Mashito
Matsumoto, Michihiro
Hamada, Shinshichi
Okamura, Hitoshi
Author's alias: 趙, 需文
土居, 雅夫
フスタ, ジャン・ミッシェル
岡村, 均
Keywords: Circadian rhythms
Issue Date: 21-Dec-2017
Publisher: Springer Nature
Journal title: Nature Communications
Volume: 8
Thesis number: 2238
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.
Description: 肝細胞の分裂に必須の時計遺伝子 --新しい分子機能を解明、肝疾患の予防や治療にも期待--. 京都大学プレスリリース. 2017-12-25.
Rights: © The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit
DOI(Published Version): 10.1038/s41467-017-02207-7
PubMed ID: 29269828
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