Distinct notch signaling expression patterns between nucleoside and nucleotide analogues treatment for hepatitis B virus infection
- Department of Gastroenterology, Kanazawa University Graduate School of Medical Science, Kanazawa (Japan)
Highlights: • Notch signaling inhibited by nucleoside analogues treatment under HBV infection. • Upregulation of Notch signaling after nucleotide analogues administration. • Reduction of Foxp3 expression by both nucleotide and nucleoside analogues treatment. • Activation of phosphorylated mTORC2–Akt cascade after nucleotide analogue treatment. Nucleos(t)ide analogues therapies are currently approved for the treatment of chronic hepatitis B virus (HBV) infection, which effectively suppress HBV replication and correlate with the anti-HBV-specific immune response. Notch signaling serves pleiotropic roles in the immune system that also contribute to virus-specific immunity. In this study, we assessed Notch signal-related gene expression after administrating nucleoside or nucleotide analogues to HBV-replicating cells and clinical liver tissues. We found distinct Notch signaling expression patterns under nucleos(t)ide analogues therapies, with high expression for nucleotide analogues (adefovir pivoxil or tenofovir disoproxil fumarate) and low expression for nucleoside analogues (lamivudine or entecavir) in the presence of HBV infection. Furthermore, activation of mammalian target of rapamycin (mTOR)-Akt (Ser473) phosphorylation was also observed after nucleotide analogue treatment. In conclusion, nucleoside and nucleotide analogues displayed different patterns of Notch signaling activity under HBV infection, and the induction of mTORC2-Akt (Ser473) phosphorylation may contribute to nucleotide analogues-mediated Notch signaling activation.
- OSTI ID:
- 23137016
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 501; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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