Hepatic stellate cells activate and avoid death under necroptosis stimuli: Hepatic fibrosis during necroptosis.
J Gastroenterol Hepatol
; 38(12): 2206-2214, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37811601
ABSTRACT
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 ANDRESULTS:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
NF-kappa B
/
Células Estreladas do Fígado
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Gastroenterol Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Coréia do Sul