TY - EJOU
AU - YOON, YONGDAE
AU - HWANG, SOONJAE
AU - SAIMA, FATEMA TUJ
AU - KIM, MOON YOUNG
AU - BAIK, SOON KOO
AU - EOM, YOUNG WOO
TI - AKT regulates IL-1β-induced proliferation and activation of hepatic stellate cells
T2 - BIOCELL
PY - 2023
VL - 47
IS - 3
SN - 1667-5746
AB - 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.
KW - Hepatic stellate cell; Interleukin-1β; AKT; Cell proliferation; Fibrosis
DO - 10.32604/biocell.2023.025365