19 research outputs found
Molecular docking performance evaluated on the D3R Grand Challenge 2015 drug-like ligand datasets
Copper sulfide nanoparticles as a photothermal switch for TRPV1 signaling to attenuate atherosclerosis
Identification of single nucleotide polymorphisms of PIK3R1 and DUSP1 genes and their genetic associations with milk production traits in dairy cows
The role of the brown adipose tissue in β3-adrenergic receptor activation-induced sleep, metabolic and feeding responses
Circadian clock regulates hepatic polyploidy by modulating Mkp1-Erk1/2 signaling pathway
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.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