文章基本信息

标题：Metabolic nuclear receptors coordinate energy metabolism to regulate Sox9 + hepatocyte fate
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作者：Shenghui Liu ; Dan Qin ; Yi Yan 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2021
卷号：24
期号：9
页码：1-25
DOI：10.1016/j.isci.2021.103003
语种：English
出版社：Elsevier
摘要：SummaryRecent research has indicated the adult liver Sox9+cells located in the portal triads contribute to the physiological maintenance of liver mass and injury repair. However, the physiology and pathology regulation mechanisms of adult liver Sox9+cells remain unknown. Here, PPARα and FXR bound to the shared site in Sox9 promoter with opposite transcriptional outputs. PPARα activation enhanced the fatty acid β-oxidation, oxidative phosphorylation (OXPHOS), and adenosine triphosphate (ATP) production, thus promoting proliferation and differentiation of Sox9+hepatocytes along periportal (PP)-perivenous (PV) axis. However, FXR activation increased glycolysis but decreased OXPHOS and ATP production, therefore preventing proliferation of Sox9+hepatocytes along PP-PV axis by promoting Sox9+hepatocyte self-renewal. Our research indicates that metabolic nuclear receptors play critical roles in liver progenitor Sox9+hepatocyte homeostasis to initiate or terminate liver injury-induced cell proliferation and differentiation, suggesting that PPARα and FXR are potential therapeutic targets for modulating liver regeneration.Graphical abstractDisplay OmittedHighlights•PPARα promotes Sox9 expression and FXR inhibits Sox9 expression•PPARα promotes proliferation and differentiation of Sox9+hepatocytes•FXR promotes Sox9+hepatocyte self-renewal•PPARα and FXR coordinate energy metabolism to regulate Sox9+hepatocyte fateHuman metabolism; Cellular physiology; Molecular physiology; Cell biology