Filamin A facilitates NLRP3 inflammasome activation during arsenic-induced nonalcoholic steatohepatitis

Prolonged exposure to arsenic can cause nonalcoholic steatohepatitis (NASH). The NOD-like receptor protein 3 (NLRP3) inflammasome plays an essential role in the process of NASH. However, the mechanism by which arsenic promotes NLRP3 expression remains unclear. Three-month NaAsO 2 gavage led to the n...

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Published in:Environmental science and pollution research international 2023-10, Vol.30 (49), p.107703-107715
Main Authors: Shi, Yan, Qiu, Tianming, Wu, Chenbing, Yuan, Weizhuo, Yao, Xiaofeng, Jiang, Liping, Wang, Ningning, Wang, Lu, Han, Qiuyue, Yang, Guang, Liu, Xiaofang, Sun, Xiance
Format: Article
Language:English
Subjects:
Aquatic Pollution
Arsenic
Atmospheric Protection/Air Quality Control/Air Pollution
Chromatin
Earth and Environmental Science
Ecotoxicology
Environment
Environmental Chemistry
Environmental Health
Fatty liver
Immunoprecipitation
Inflammasomes
NF-κB protein
Pyroptosis
Research Article
Signal transduction
siRNA
Sodium arsenite
Translocation
Waste Water Technology
Water Management
Water Pollution Control
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Summary:Prolonged exposure to arsenic can cause nonalcoholic steatohepatitis (NASH). The NOD-like receptor protein 3 (NLRP3) inflammasome plays an essential role in the process of NASH. However, the mechanism by which arsenic promotes NLRP3 expression remains unclear. Three-month NaAsO 2 gavage led to the nuclear factor-κB (NF-κB) signaling pathway activation and NASH. Additionally, NaAsO 2 upregulated the level of Filamin A (FLNA) and pyroptosis, thereby activating the NLRP3 inflammasome in SD rat liver. Using FLNA siRNA, NASH-associated inflammation and pyroptosis were clearly mitigated by reducing activation of the NLRP3 inflammasome. Furthermore, arsenic treatment facilitated activation of the NF-κB signaling pathway and promoted p-p65 translocation into the nucleus. Chromatin immunoprecipitation (Ch-IP) assay indicated that FLNA promoted p65 binding to the NLRP3 gene and upregulated the transcription of NLRP3, ultimately leading to pyroptosis and NASH. Our findings indicate that FLNA and pyroptosis are strongly associated with NASH induced by NaAsO 2 . Collectively, the findings of this study indicated that FLNA mediates NF-κB signaling pathway-induced activation of the NLRP3 inflammasome and ultimately activates pyroptosis and NASH upon NaAsO 2 exposure. This information may be useful for improving therapeutic strategies against arsenic-induced NASH. Graphical abstract
ISSN:1614-7499
0944-1344
1614-7499
DOI:10.1007/s11356-023-29702-3