SERP1 reduces inchoate acute hepatic injury through regulation of endoplasmic reticulum stress via the GSK3ß/ßcatenin/TCF/LEF signaling pathway.
Mol Med Rep
; 25(6)2022 Jun.
Article
em En
| MEDLINE
| ID: mdl-35419615
ABSTRACT
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 stressassociated endoplasmic reticulum protein 1 (SERP1) in acute hepatic injury. Mice were injected intraperitoneally with Dgalactosamine/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 transcriptionquantitative 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 GSK3ß/ßcatenin/Tcell factor (TCF)/lymphoid enhancing factor (LEF) signaling pathway. In addition, a GSK3ß overexpression plasmid was constructed to investigate the role of GSK3ß/ßcatenin 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, apoptosisrelated proteins and ERSrelated proteins, as well as the expression of proteins related to GSK3ß/ßcatenin/TCF/LEF signaling pathways. A GSK3ß overexpression plasmid was constructed and it was revealed that GSK3ß overexpression could reverse the effects of SERP1 overexpression in aforementioned aspects. This suggested that the activation of the GSK3ß/ßcatenin/TCF/LEF signaling pathway may be required for the regulation of SERP1. In conclusion, SERP1 regulated ERS via the GSK3ß/ßcatenin/TCF/LEF signaling pathway, thereby reducing inchoate acute hepatic injury.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Beta Catenina
/
Estresse do Retículo Endoplasmático
/
Proteínas de Membrana
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article