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

Cai,Jie; Sun,Zhenhua; Zhang,Lili; Xu,Hongrui

doi:10.3892/mmr.2022.12709

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

Authors:
- Jie Cai
- Zhenhua Sun
- Lili Zhang
- Hongrui Xu
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Affiliations: Department of Infectious Disease, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Translational Medicine Center, Huaihe Hospital of Henan University, Kaifeng, Henan 475000, P.R. China
Published online on: April 6, 2022 https://doi.org/10.3892/mmr.2022.12709
Article Number: 193
Copyright: © Cai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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 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 GSK3β/β‑catenin/T‑cell factor (TCF)/lymphoid enhancing factor (LEF) signaling pathway. In addition, a GSK3β overexpression plasmid was constructed to investigate the role of GSK3β/β‑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 GSK3β/β‑catenin/TCF/LEF signaling pathways. A GSK3β overexpression plasmid was constructed and it was revealed that GSK3β overexpression could reverse the effects of SERP1 overexpression in aforementioned aspects. This suggested that the activation of the GSK3β/β‑catenin/TCF/LEF signaling pathway may be required for the regulation of SERP1. In conclusion, SERP1 regulated ERS via the GSK3β/β‑catenin/TCF/LEF signaling pathway, thereby reducing inchoate acute hepatic injury.

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