SERP1 reduces inchoate acute hepatic injury through regulation of endoplasmic reticulum stress via the GSK3β/β-catenin/TCF/LEF signaling pathway

The liver is a crucial digestive organ of humans and in charge of detoxification. Acute hepatic injury is an aggressive type of hepatic disease and its harmful effect cannot be ignored. The present study examined the role and mechanism of stress-associated endoplasmic reticulum protein 1 (SERP1) in acute hepatic injury. Mice were injected intraperitoneally with D-galactosamine/lipopolysaccharide (LPS) and rat hepatocytes were induced by LPS to establish an acute hepatic injury model. Tissue lesions were observed by H & E staining, and biomarkers of hepatic injury in the serum were examined. Western blotting, immunohistochemistry and reverse transcription-quantitative PCR were performed to assess SERP1 expression in tissues and hepatocytes. A SERP1 overexpression plasmid was constructed to evaluate the role of SERP1 in inflammation, apoptosis, endoplasmic reticulum stress (ERS) and the GSK3 beta/beta-catenin/T-cell factor (TCF)/lymphoid enhancing factor (LEF) signaling pathway. In addition, a GSK3 beta overexpression plasmid was constructed to investigate the role of GSK3 beta/beta-catenin signal activation. Additionally, the present study investigated whether SERP1 regulated the endoplasmic reticulum via this pathway. In the present study, reliable animal and cellular hepatic injury models were established and verified. SERP1 overexpression reduced the expression of inflammatory factors, apoptosis-related proteins and ERS-related proteins, as well as the expression of proteins related to GSK3 beta/beta-catenin/TCF/LEF signaling pathways. A GSK3 beta overexpression plasmid was constructed and it was revealed that GSK3 beta overexpression could reverse the effects of SERP1 overexpression in aforementioned aspects. This suggested that the activation of the GSK3 beta/beta-catenin/TCF/LEF signaling pathway may be required for the regulation of SERP1. In conclusion, SERP1 regulated ERS via the GSK3 beta/beta-catenin/TCF/LEF signaling pathway, thereby reducing inchoate acute hepatic injury.

Automated summary

This study investigated the role and mechanism of SERP1 in acute hepatic injury, finding that SERP1 regulates endoplasmic reticulum stress through the GSK3 beta/beta-catenin/TCF/LEF signaling pathway, reducing the occurrence of inchoate acute hepatic injury.