| First Author | Wu MS | Year | 2021 |
| Journal | Am J Pathol | Volume | 191 |
| Issue | 6 | Pages | 1036-1048 |
| PubMed ID | 33753025 | Mgi Jnum | J:308496 |
| Mgi Id | MGI:6729822 | Doi | 10.1016/j.ajpath.2021.03.006 |
| Citation | Wu MS, et al. (2021) Type I Interferon Signaling Accelerates Liver Regeneration by Metabolic Modulation in Noninfectious Conditions. Am J Pathol 191(6):1036-1048 |
| abstractText | Type I interferon (IFN-I) has a well-known function in controlling viral infections, but its contribution in hepatocyte proliferation and hepatocellular carcinoma (HCC) formation remains unclear. Mice deficient in IFN-alpha receptor expression in whole mice or only in hepatocytes (Ifnar(-/-) and Ifnar(Deltaliver)) were used to investigate the role of IFN-I signaling in cell proliferation and cancer formation in the liver. Ifnar(-/-) mice were resistant to chemical-induced HCC formation in the absence of infection. The results show that low grade of IFN-I and interferon-stimulated gene were expressed substantially in naive mouse liver. The low level of IFN-I activation is constantly present in mouse liver after weaning and negatively modulates forkhead box O hepatic expression. The IFN-I signaling can be partially blocked by the clearance of lipopolysaccharide. Mice lacking IFN-I signaling have lower basal proliferation activity and delayed liver regeneration processes after two-thirds partial hepatectomy. The activation of IFN-I signaling on hepatocyte controls glucose homeostasis and lipid metabolism to support proliferation potency and long-term tumorigenesis. Our results reveal a positive role of low-grade IFN-I singling to hepatocyte proliferation and HCC formation by modulating glucose homeostasis and lipid metabolism. |
