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Knockdown of Astrocyte Elevated Gene-1 Inhibits Activation of Hepatic Stellate Cells

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Abstract

Background

Astrocyte elevated gene-1 (AEG-1) is a positive regulator of tumorigenesis and a valuable prognostic marker of a diverse array of cancers, including liver cancer; however, the relationship between AEG-1 and hepatic fibrogenesis is not known.

Objective

The objective of this study was to explore the expression of AEG-1 during hepatic fibrogenesis and determine how AEG-1 regulates the profibrogenic phenotype of hepatic stellate cells (HSCs).

Methods

The levels of AEG-1 were monitored in the fibrotic livers and transforming growth factor-β (TGF-β)- or lipopolysaccharide (LPS)-stimulated HSCs. The expression of AEG-1 was knocked down by lentivirus-mediated short hairpin RNA in HSCs, and collagen expression, proliferation assays, apoptosis induction studies, and migration assays were simultaneously conducted in vitro.

Results

AEG-1 expression was increased in the fibrotic livers. At the cellular level, TGF-β or LPS stimulation, which caused HSC activation, induced AEG-1 expression in HSC-T6 and primary rat HSCs (P < 0.05). Knockdown of AEG-1 inhibited collagen I and α-smooth muscle actin expression (P < 0.05), reduced cell proliferation (P < 0.05) and motility (P < 0.05), and induced cell apoptosis (P < 0.05) in HSCs. This antifibrotic effect caused by lack of AEG-1 was associated with the inactivation of PI3K/Akt and the mitogen-activated protein kinase pathway.

Conclusions

Knockdown of AEG-1 suppressed the activation of HSCs by modulating the phenotype and inducing apoptosis. AEG-1 might be a potential target in treatment of hepatic fibrosis.

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Acknowledgment

This study was supported by the National Natural Science Foundation of China (No. 81170411).

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Authors and Affiliations

  1. Department of Gastroenterology, The Second Hospital of Hebei Medical University, Hebei Key Laboratory of Gastroenterology, Hebei Institute of Gastroenterology, No. 215, Heping West Road, Shijiazhuang, 050000, Hebei Province, China

    Lei Chen, Yong-ze Guo, Ai-di Li, Jun-ji Ma, Di Zhang, Yan Wang, Chen-guang Ji, Wei Qi, Jia Wang & Hui-qing Jiang

  2. Department of Endocrinology and Metabolism, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, China

    Hui-yao Hao

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  1. Lei Chen
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Correspondence to Hui-qing Jiang.

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Chen, L., Guo, Yz., Li, Ad. et al. Knockdown of Astrocyte Elevated Gene-1 Inhibits Activation of Hepatic Stellate Cells. Dig Dis Sci 61, 1961–1971 (2016). https://doi.org/10.1007/s10620-016-4075-8

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  • DOI: https://doi.org/10.1007/s10620-016-4075-8

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