| First Author | Liu S | Year | 2021 |
| Journal | iScience | Volume | 24 |
| Issue | 9 | Pages | 103003 |
| PubMed ID | 34505013 | Mgi Jnum | J:313519 |
| Mgi Id | MGI:6798036 | Doi | 10.1016/j.isci.2021.103003 |
| Citation | Liu S, et al. (2021) Metabolic nuclear receptors coordinate energy metabolism to regulate Sox9(+) hepatocyte fate. iScience 24(9):103003 |
| abstractText | Recent 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, PPARalpha and FXR bound to the shared site in Sox9 promoter with opposite transcriptional outputs. PPARalpha activation enhanced the fatty acid beta-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 PPARalpha and FXR are potential therapeutic targets for modulating liver regeneration. |
