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

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.