Research ArticleLiver disease

Hepatocyte Notch activation induces liver fibrosis in nonalcoholic steatohepatitis

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Science Translational Medicine  21 Nov 2018:
Vol. 10, Issue 468, eaat0344
DOI: 10.1126/scitranslmed.aat0344

Taking liver fibrosis down a Notch

Nonalcoholic steatohepatitis (NASH) is a liver disease characterized by fat accumulation, inflammation, and liver cell damage. Here, Zhu et al. focused on Notch signaling in NASH and associated liver fibrosis. Expression of Notch target genes was increased in liver biopsies from patients with more severe NASH, and a mouse model of diet-induced NASH showed increased hepatocyte Notch expression. Notch signaling activated hepatic stellate cells, leading to liver fibrosis. Inhibiting Notch signaling using a liver-targeted antisense oligonucleotide reduced liver fibrosis in a diet-induced NASH mouse model. This study suggests that targeting hepatocyte Notch signaling could be therapeutic for NASH-associated liver fibrosis.

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