Hexafluoropropylene oxide trimer acid exposure triggers necroptosis and inflammation through the Wnt/β-catenin/NF-κB axis in the liver

Hexafluoropropylene oxide trimer acid (HFPO-TA), an emerging alternative to perfluorooctanoic acid (PFOA), has recently been identified as a significant environmental pollutant. Nevertheless, there is a scarcity of studies regarding the hepatotoxic effects of HFPO-TA. Here, we investigated the types...

Full description

Saved in:
Bibliographic Details
Published in:The Science of the total environment 2023-12, Vol.905, p.167033, Article 167033
Main Authors: Zhang, Xuliang, Li, Bo, Huo, Siming, Du, Jiayu, Zhang, Jian, Song, Miao, Shao, Bing, Li, Yanfei
Format: Article
Language:English
Subjects:
HFPO-TA
Inflammation
Liver
Necroptosis
W/β/NF-κB axis
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Hexafluoropropylene oxide trimer acid (HFPO-TA), an emerging alternative to perfluorooctanoic acid (PFOA), has recently been identified as a significant environmental pollutant. Nevertheless, there is a scarcity of studies regarding the hepatotoxic effects of HFPO-TA. Here, we investigated the types and potential mechanisms of liver damage caused by HFPO-TA. Initially, we validated that the introduction of HFPO-TA resulted in the Wnt/β-catenin signaling (W/β signaling) activation, as well as the induction of necroptosis and inflammation, both in the liver of mice and in HepG2 cells. Subsequently, we established that the W/β signaling mediated the necroptosis and inflammation observed in the liver and HepG2 cells exposed to HFPO-TA. Finally, we demonstrated that the phosphorylated form of NF-κB p65 (p-NF-κB p65) played a role in mediating the necroptosis and inflammation, and its activity could be regulated by the W/β signaling pathway in the liver of mice and HepG2 cells exposed to HFPO-TA. In conclusion, our investigation elucidates the role of HFPO-TA in inducing necroptosis and inflammation in the liver, which is facilitated through the activation of the W/β/NF-κB axis. [Display omitted] •HFPO-TA induced necroptosis and inflammation in liver, both in vitro and in vivo.•Wnt/β-catenin promotes the translocation of p-NF-κB p65 into the nucleus.•Wnt/β-catenin/NF-κB axis mediates HFPO-TA-induced liver injury.
ISSN:0048-9697
1879-1026
1879-1026
DOI:10.1016/j.scitotenv.2023.167033