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REVIEW article

Front. Med.

Sec. Pathology

Dynamic Dual Regulation of Amphiregulin in Liver Pathophysiology: Balancing Regeneration and Disease Progression via the EGFR Axis

    YW

    yili Wang 1

    DZ

    dejiang Zhou 2

    QW

    qiongwan Wang 3

    YZ

    ye Zhang 3

    WY

    wenjing Yang 3

    WT

    wenjie Tan 3

    HW

    haoyu Wang 3

    SL

    Sanqiang Li 4,3

  • 1. The First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China

  • 2. North Henan Medical University, Xinxiang, China

  • 3. Henan University of Science and Technology School of Basic Medicine and Forensic Medicine, Luoyang, China

  • 4. Henan University of Science and Technology, Luoyang, China

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Abstract

Liver diseases, ranging from acute injury to chronic fibrosis and hepatocellular carcinoma (HCC), represent a major global health challenge with limited therapeutic options. The liver’s inherent regenerative capacity can be disrupted during chronic disease, resulting in poor outcomes. However, this process is complex, as key regulatory molecules can exert opposite effects. A notable example is Amphiregulin (AREG), an epidermal growth factor receptor (EGFR) ligand whose role changes from promoting protective regeneration in acute injury to driving harmful processes in chronic settings. This review explores the dual and dynamic roles of AREG across the spectrum of liver diseases, with a focus on its expression patterns, downstream molecular pathways, and signaling networks that determine its functional transition from regeneration to fibrosis and carcinogenesis. These insights provide new theoretical foundations and potential intervention strategies for targeting the AREG-EGFR axis in liver disease therapeutics.

Summary

Keywords

amphiregulin, Cancer, Epidermal Growth Factor, Liver, liver fibrosis

Received

03 September 2025

Accepted

03 February 2026

Copyright

© 2026 Wang, Zhou, Wang, Zhang, Yang, Tan, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Sanqiang Li

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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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