2. Academic Validation
  3. Co-Exposure to Polystyrene Microplastics and Bisphenol A Contributes to the Formation of Liver Fibrosis in Mice through Inhibition of the BMAL1/E-Cad Signaling Pathway

Co-Exposure to Polystyrene Microplastics and Bisphenol A Contributes to the Formation of Liver Fibrosis in Mice through Inhibition of the BMAL1/E-Cad Signaling Pathway

  • J Agric Food Chem. 2025 Mar 26;73(12):7405-7422. doi: 10.1021/acs.jafc.4c08790.
Bonan Xiao 1 2 3,  Wanghao Yang 1 2 3,  Hao Dong 1 2 3,  Tian Liu 1 2 3,  Chao Li 1 2 3,  Yiqun Wang 1 2 3,  Dengke Gao 1 2 3,  Guohao Han 1 2 3,  Fouzia Kiran 1 2 3,  Aihua Wang 3 4,  Yaping Jin 1 2 3,  Yalin Yuan 1,  Huatao Chen 1 2 3
Affiliations

Affiliations

  • 1 Northwest A&F University, Yangling, Shaanxi 712100, China.
  • 2 Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • 3 Key Laboratory of Animal Biotechnology of the Ministry of Agriculture and Rural Affairs, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • 4 Department of Preventative Veterinary Medicine, College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi 712100, China.
PMID: 40073227 DOI: 10.1021/acs.jafc.4c08790
Abstract

The food safety risks posed by exposure to polystyrene microplastics (PS-MPs) and bisphenol A (BPA) have become an issue worldwide. However, the toxic effects of PS-MPs and BPA coexposure on the mammalian liver remain elusive. In this study, we found that PS-MPs and BPA coexposure have synergistic toxic effects on AML12 cells and the mouse liver. Histopathological staining revealed excessive accumulation of the extracellular matrix in the coexposure liver. Co-exposure to PS-MPs and BPA downregulated Bmal1 and E-cad both in vitro and in vivo. Additionally, Bmal1-/- AML12 cells and liver-specific Bmal1-/- mice exhibited significantly reduced E-cad levels, with no significant reduction under PS-MPs and BPA coexposure. Notably, overexpression of BMAL1 and CLOCK significantly enhanced luciferase activity driven by the E-cad gene intron region (containing an E-box cis-element). These results demonstrated that coexposure to PS-MPs and BPA contributed to the development of liver fibrosis by inhibiting the BMAL1/E-cad signaling pathway.

Keywords

E-cad; bisphenol A; circadian clock; liver fibrosis; polystyrene microplastics.

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