2. Academic Validation
  3. PFPeA exposure drives hepatoxicity and liver fibrosis via oxidative stress/Wnt5a-induced hepatocyte senescence

PFPeA exposure drives hepatoxicity and liver fibrosis via oxidative stress/Wnt5a-induced hepatocyte senescence

  • J Hazard Mater. 2026 Feb 1:503:141085. doi: 10.1016/j.jhazmat.2026.141085.
Kaijie Ren 1,  Yuanchang Peng 1,  Huan Chen 2,  Xueni Wang 3,  Tianhao Min 1,  Yuyi Ma 1,  Xiaoyuan Deng 1,  Shiyao Tong 1,  Yuanyuan Liu 1,  Yong Zhang 1,  Kun Zhu 1,  Chengxue Dang 1,  Benhua Sun 4,  Hao Zhang 5,  Wei Wang 6,  Tuanhe Sun 7
Affiliations

Affiliations

  • 1 Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
  • 2 Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
  • 3 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
  • 4 College of Natural Resources and Environment, Northwest A&F University, Key Laboratory of Green and Low Carbon Agriculture on Dryland in Northwest China, Ministry of Agriculture and Rural Affairs, Yangling, Shaanxi 712100, China.
  • 5 Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Clinical Medicine and Cancer Research Center of Shaanxi Province, Xi'an, Shaanxi 710061, China.
  • 6 Department of Obstetrics and Gynecology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: [email protected].
  • 7 Department of Surgical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: [email protected].
PMID: 41529635 DOI: 10.1016/j.jhazmat.2026.141085
Abstract

Perfluoropentanoic acid (PFPeA), one of short-chain PFASs, has raised concern due to existence in the environment. The hepatotoxicity of PFPeA remains to be further elucidated. Cellular senescence, a distinct cellular state that occurs under stress conditions, plays a vital role in the progression of various diseases. However, the contribution of cellular senescence to PFPeA induced liver toxicity remains unclear. Our study investigated the specific role of cellular senescence in PFPeA induced liver injury and its underlying mechanisms in C57BL/6 J mice and THLE-2 cells. Our results demonstrated that PFPeA exposure at 5 μg/ml significantly induces hepatocyte senescence and liver injury, and fibrosis in mice. Further experiments revealed that PFPeA triggers excessive ROS production in hepatocytes, which leads to sustained activation of the Wnt5a signaling pathway, subsequently inducing cellular senescence and senescence-associated secretory phenotype (SASP) secretion, and ultimately resulting in liver dysfunction and fibrosis. Combination therapy targeting both senescence and Wnt5a significantly alleviated PFPeA -induced liver injury. In summary, our study provides compelling evidence highlighting the important role of cellular senescence in PFPeA induced liver injury. This research broadens our understanding of PFPeA induced hepatotoxicity and provides potential therapeutic and preventive strategies for managing PFPeA-related liver injury.

Keywords

Cellular senescence; Hepatoxicity; PFPeA; Wnt5a.

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