# Dynamic dual regulation of amphiregulin in liver pathophysiology: balancing regeneration and disease progression via the EGFR axis

## TL;DR

Amphiregulin (AREG) plays a dual role in liver diseases, switching from aiding regeneration to promoting disease progression, offering new therapeutic insights.

## Contribution

This paper reviews the dynamic regulatory role of AREG in liver pathophysiology, highlighting its transition from regeneration to disease.

## Key findings

- AREG promotes liver regeneration in acute injury but contributes to fibrosis and cancer in chronic conditions.
- The AREG-EGFR axis is a potential therapeutic target for liver disease intervention.
- Expression patterns and signaling networks of AREG determine its functional shift in liver pathogenesis.

## 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.