Stimulated hepatic stellate cell promotes progression of hepatocellular carcinoma due to protein kinase R activation

PloS One
Yusuke ImaiYoichi Hiasa

Abstract

Hepatic stellate cells (HSCs) were reported to promote the progression of hepatocellular carcinoma (HCC), however its mechanism is uncertain. We previously reported that protein kinase R (PKR) in hepatocytes regulated HCC proliferation. In this study, we focused on the role of PKR in HSCs, and clarified the mechanism of its association with HCC progression. We confirmed the activation of PKR in a human HSC cell line (LX-2 cell). IL-1β is produced from HSCs stimulated by lipopolysaccharide (LPS) or palmitic acid which are likely activators of PKR in non-alcoholic steatohepatitis (NASH). Production was assessed by real-time PCR and ELISA. C16 and small interfering RNA (siRNA) were used to inhibit PKR in HSCs. The HCC cell line (HepG2 cell) was cultured with HSC conditioning medium to assess HCC progression, which was evaluated by proliferation and scratch assays. Expression of PKR was increased and activated in stimulated HSCs, and IL-1β production was also increased molecular. Key molecules of the mitogen-activated protein kinase pathway were also upregulated and activated by LPS. Otherwise, PKR inhibition by C16 and PKR siRNA decreased IL-1β production. HCC progression was promoted by HSC-stimulated conditioning medium although...Continue Reading

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Citations

Apr 12, 2019·International Journal of Molecular Sciences·Antonio SircanaGiovanni Musso
Nov 13, 2019·European Journal of Pharmacology·Liang-Yun LiTao Xu
Feb 25, 2020·Current Molecular Pharmacology·Mengna WuWenjie Zheng
Jan 14, 2022·The Journal of Immunology : Official Journal of the American Association of Immunologists·Wenting LiWenyu Lin

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Datasets Mentioned

BETA
NM002759

Methods Mentioned

BETA
Enzyme-linked Immunosorbent Assay
ELISA

Software Mentioned

Axio Vision
JMP

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