Open Access
ARTICLE
AKT regulates IL-1β-induced proliferation and activation of hepatic stellate cells
YONGDAE YOON1,#, SOONJAE HWANG1,2,#, FATEMA TUJ SAIMA3,#, MOON YOUNG KIM1,3,4, SOON KOO BAIK1,3,4,*, YOUNG WOO EOM1,3,*
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:
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
Cite This Article
YOON, Y., HWANG, S., SAIMA, F. T., KIM, M. Y., BAIK, S. K. et al. (2023). AKT regulates IL-1β-induced proliferation and activation of hepatic stellate cells.
BIOCELL, 47(3), 669–676. https://doi.org/10.32604/biocell.2023.025365