Hepatic stellate cells activate and avoid death under necroptosis stimuli: Hepatic fibrosis during necroptosis.

Autor: Oh JH; Department of Obstetrics and Gynecology, Institute of Women's Medical Life Science, Yonsei Cancer Center, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea., Saeed WK; Department of Biomedical Sciences, Pak-Austria Fachhochschule: Institute of Applied Sciences and Technology, Haripur, Pakistan., Kim HY; Department of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea., Lee SM; Department of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea., Lee AH; Department of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea., Park GR; Department of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea., Yoon EL; Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, South Korea., Jun DW; Department of Translational Medicine, Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea.
Jazyk: angličtina
Zdroj: Journal of gastroenterology and hepatology [J Gastroenterol Hepatol] 2023 Dec; Vol. 38 (12), pp. 2206-2214. Date of Electronic Publication: 2023 Oct 09.
DOI: 10.1111/jgh.16368
Abstrakt: Background and Aim: Necroptosis is an emerging cell death pathway that allows cells to undergo "cellular suicide" in a caspase-independent manner. We investigated the fate of hepatic stellate cells (HSCs) under necroptotic stimuli.
Methods and Results: The RNA level of mixed lineage kinase domain-like protein (MLKL) is higher in patients with non-alcoholic fatty liver disease than in healthy controls. Hepatic fibrosis was significantly lower in MLKL-KO bile duct ligation (KO-BDL) mice than in wild-type-BDL mice. Necroptotic stimuli caused the death of HT-29 and U937 cells. However, necroptotic stimuli activate HSCs instead of inducing cell death. MLKL inhibitors attenuated fibrogenic changes in HSCs during necroptosis. Unlike HT-29 and U937 cells, MLKL phosphorylation and oligomerization were not observed during necroptosis in HSCs. RNA sequencing showed that NF-κB signaling-related genes were upregulated in HSCs following necroptotic stimulation. Necroptotic stimuli in HSCs increased the nuclear expression of NF-κB, which decreased after MLKL inhibitor treatment. Induction of necroptosis in HSCs led to autophagosome activation and formation, which were attenuated by MLKL inhibitor treatment.
Conclusion: HSCs avoid necroptosis due to the absence of MLKL phosphorylation and oligomerization and are activated through autophagosome and NF-κB pathways.
(© 2023 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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