2. Academic Validation
  3. Hyperphosphorylation of EGFR/ERK signaling facilitates long-term arsenite-induced hepatocytes epithelial-mesenchymal transition and liver fibrosis in sprague-dawley rats

Hyperphosphorylation of EGFR/ERK signaling facilitates long-term arsenite-induced hepatocytes epithelial-mesenchymal transition and liver fibrosis in sprague-dawley rats

  • Ecotoxicol Environ Saf. 2022 Dec 9;249:114386. doi: 10.1016/j.ecoenv.2022.114386.
Dapeng Wang 1,  Huifen Xu 2,  Lili Fan 2,  Wenli Ruan 3,  Qian Song 2,  Heng Diao 2,  Rui He 2,  Ying Jin 2
Affiliations

Affiliations

  • 1 Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, Guizhou, China. Electronic address: [email protected].
  • 2 Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, Guizhou, China.
  • 3 Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Department of Toxicology, School of Public Health, Guizhou Medical University, Guiyang 550025, Guizhou, China; Tongren Center for Disease Control and Prevention, Tongren 554300, Guizhou, China.
PMID: 36508792 DOI: 10.1016/j.ecoenv.2022.114386
Abstract

Arsenic is a well known environmental hazardous material, chronic arsenic exposure results in different types of liver damage. Among them, liver fibrosis has become a research hotspot because of its reversibility, while the underlying mechanism is still unclear. Previous studies revealed that EGFR/ERK signaling appears to play an important role in fibrosis diseases. In this study, sprague-dawley rats were exposed to different doses of arsenite for 36 weeks to investigate the roles of EGFR/ERK signaling on arsenite-induced liver fibrogenesis. Our results showed that long-term arsenite exposure induced liver fibrosis, accompanied by hepatic stellate cells (HSCs) activation, excessive serum secretion of extracellular matrix (ECM), and hepatocytes epithelial-mesenchymal transformation (EMT). In addition, arsenite exposure caused hyperphosphorylation of EGFR/ERK signaling in liver tissue of rats, indicating that EGFR/ERK signaling may be involved in arsenite-induced liver fibrosis. Indeed, erlotinib (a specific phosphorylation inhibitor of EGFR) intervention significantly decreased arsenite induced hyperphosphorylation of EGFR/ERK signaling, thereby suppressed hepatocytes EMT process and alleviated liver fibrogenesis in arsenite exposed rats. In summary, the present study provides evidences showing that hyperphosphorylation of EGFR/ERK signaling facilitates long-term arsenite-induced hepatocytes EMT and liver fibrosis in rats, which brings new insights into the pathogenesis of arsenic-induced liver injury.

Keywords

Arsenic; Epidermal growth factor receptor; Epithelial-mesenchymal transition; Liver fibrosis; Phosphorylation.

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