Long-term exposure to polychlorinated biphenyl 126 induces liver fibrosis and upregulates miR-155 and miR-34a in C57BL/6 mice

PLoS One. 2024 Aug 12;19(8):e0308334. doi: 10.1371/journal.pone.0308334. eCollection 2024.

Abstract

Environmental pollutants, including polychlorinated biphenyls (PCBs), act as endocrine disruptors and impair various physiological processes. PCB 126 is associated with steatohepatitis, fibrosis, cirrhosis, and other hepatic injuries. These disorders can be regulated by microRNAs (miRNAs). Therefore, this study aimed to investigate the role of miRNAs in non-alcoholic fatty liver disease associated with exposure to PCB 126. Adult male C57BL/6 mice were exposed to PCB 126 (5 μmol/kg of body weight) for 10 weeks. The PCB group showed lipid accumulation in the liver in the presence of macro- and microvesicular steatosis and fibrosis with increased inflammatory and profibrotic gene expression, consistent with non-alcoholic steatohepatitis (NASH). PCB exposure also upregulated miR-155 and miR-34a, which induce the expression of proinflammatory cytokines and inflammation in the liver and reduce the expression of peroxisome proliferator-activated receptor α, which, in turn, impairs lipid oxidation and hepatic steatosis. Therefore, the present study showed that PCB 126 induced NASH via potential mechanisms involving miR-155 and miR-34a, which may contribute to the development of new diagnostic markers and therapeutic strategies.

MeSH terms

  • Animals
  • Environmental Pollutants / toxicity
  • Lipid Metabolism / drug effects
  • Lipid Metabolism / genetics
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis* / chemically induced
  • Liver Cirrhosis* / genetics
  • Liver Cirrhosis* / metabolism
  • Liver Cirrhosis* / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Non-alcoholic Fatty Liver Disease / chemically induced
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / metabolism
  • Non-alcoholic Fatty Liver Disease / pathology
  • Polychlorinated Biphenyls* / toxicity
  • Up-Regulation* / drug effects

Substances

  • MicroRNAs
  • Polychlorinated Biphenyls
  • MIRN34a microRNA, mouse
  • Mirn155 microRNA, mouse
  • 3,4,5,3',4'-pentachlorobiphenyl
  • Environmental Pollutants

Grants and funding

This research was supported by the Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro-FAPERJ (grant numbers E-26/211.193/202, E-26/201.234/2022, and E-26/210.332/2022) and the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES, 001.