Angiotensin II can trigger HSC-LX2 pyroptosis through both classical and non-classical pathways.
Life Sci
; 307: 120878, 2022 Oct 15.
Article
em En
| MEDLINE
| ID: mdl-35961596
BACKGROUND: Current evidence suggests that liver fibrosis is reversible even at late stages. Pyroptosis is reportedly regulated by classical and non-classical pathways and is also involved in the activation of the human hepatic stellate cell line LX2. This study sought to identify regulatory pathways that pyroptosis of HSC during AngII-ROS-induced HSC activation and provides novel insights for anti-fibrosis therapy by targeting HSC. MATERIALS AND METHODS: All experiments were conducted in HSC-LX2. The expressions of α-SMA, NLRP3, Caspases-1, -4, -5, ASC and GSDMD-N were detected in HSC-LX2 cells induced with AngII by Western blot and qRT-PCR. CCK8 was used to detect cell proliferation and activity. 2'-7'dichlorofluorescin diacetate (DCFH-DA) was used to measure ROS generation. An LDH assay kit was used to detect LDH released from damaged cells, and ELISA was used to quantify IL-18 and IL-1ß levels. RESULTS: After AngII stimulation, HSC-LX2 cell viability, ROS, LDH, IL-18, and IL-1ß were increased compared with Control group. At the same time, the protein and mRNA levels of α-SMA, NLRP3, Caspases-1, -4, -5, ASC and GSDMD-N were increased. In addition, after NAC and NSA treatment, LDH, IL-18 and IL-1ß levels and the protein and mRNA expression of α-SMA, Caspases-4 and -5, and GSDMD-N were decreased. CONCLUSION: HSC-LX2 pyroptosis induced by AngII-ROS is mediated by the classical pathway involving NLRP3/Caspase-1 and the non-classical pathway involving Caspases-4 and -5. Our results provide compelling evidence that AngII could activate Caspases-4 and -5 by producing ROS.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piroptose
/
Proteína 3 que Contém Domínio de Pirina da Família NLR
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Life Sci
Ano de publicação:
2022
Tipo de documento:
Article