Open Access

ARTICLE

AKT regulates IL-1β-induced proliferation and activation of hepatic stellate cells

by YONGDAE YOON^1,#, SOONJAE HWANG^1,2,#, FATEMA TUJ SAIMA^3,#, MOON YOUNG KIM^1,3,4, SOON KOO BAIK^1,3,4,*, YOUNG WOO EOM^1,3,*

1 Regeneration Medicine Research Center, Yonsei University Wonju College of Medicine, Wonju, 26426, Korea
2 Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute, GAIST, Gachon University College of Medicine, Incheon, 21999, Korea
3 Cell Therapy and Tissue Engineering Center, Yonsei University Wonju College of Medicine, Wonju, 26426, Korea
4 Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, 26426, Korea

* Corresponding Authors: SOON KOO BAIK. Email: ; YOUNG WOO EOM. Email:
# These authors contributed equally to this work

BIOCELL 2023, 47(3), 669-676. https://doi.org/10.32604/biocell.2023.025365

Received 07 July 2022; Accepted 06 September 2022; Issue published 03 January 2023

Abstract

Background: Activated hepatic stellate cells (HSCs) are closely involved in the initiation, perpetuation, and resolution of liver fibrosis. Pro-inflammatory cytokine levels are positively correlated with the transition from liver injury to fibrogenesis and contribute to HSC pathophysiology in liver fibrosis. Methods: In this study, we investigated the effect of the pro-inflammatory cytokine interleukin (IL)-1β on the proliferation and signaling pathways involved in fibrogenesis in LX-2 cells, an HSC cell line, using western blotting and cell proliferation assays. Results: IL-1β increased the proliferation rate and α-smooth muscle actin (SMA) expression of LX-2 cells in a dose-dependent manner. Within 1 h after IL-1β treatment, c-Jun N-terminal kinase (JNK), p38, and nuclear factor-κB (NF-κB) signaling was activated in LX-2 cells. Subsequently, protein kinase B (AKT) phosphorylation and an increase in α- SMA expression were observed in LX-2 cells. Each inhibitor of JNK, p38, or NF-κB decreased cell proliferation, AKT phosphorylation, and α-SMA expression in IL-1β-treated LX-2 cells. Conclusion: These results indicate that JNK, p38, and NF-κB signals converge at AKT phosphorylation, leading to LX-2 activation by IL-1β. Therefore, the AKT signaling pathway can be used as a target for alleviating liver fibrosis by the inflammatory cytokine IL-1β.

---

Keywords

---