{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T13:03:47Z","timestamp":1771419827427,"version":"3.50.1"},"reference-count":83,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2023 Henan Province Central Guidance and Local Science and Technology Development Fund","award":["Z20231811030"],"award-info":[{"award-number":["Z20231811030"]}]},{"name":"Basic Research Project of Key Scientific Research Projects of Universities in Henan Province","award":["23ZX006"],"award-info":[{"award-number":["23ZX006"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>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\u2019s 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.<\/jats:p>","DOI":"10.3389\/fmed.2026.1697954","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T12:12:04Z","timestamp":1771416724000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Dynamic dual regulation of amphiregulin in liver pathophysiology: balancing regeneration and disease progression via the EGFR axis"],"prefix":"10.3389","volume":"13","author":[{"given":"Yi-Li","family":"Wang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, Henan, China"]},{"name":"The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology","place":["Luoyang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De-Jiang","family":"Zhou","sequence":"additional","affiliation":[{"name":"North Henan Medical University","place":["Xinxiang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong-Wan","family":"Wang","sequence":"additional","affiliation":[{"name":"The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology","place":["Luoyang, Henan, China"]},{"name":"Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases","place":["Luoyang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology","place":["Luoyang, Henan, China"]},{"name":"Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases","place":["Luoyang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology","place":["Luoyang, Henan, China"]},{"name":"Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases","place":["Luoyang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Jie","family":"Tan","sequence":"additional","affiliation":[{"name":"The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology","place":["Luoyang, Henan, China"]},{"name":"Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases","place":["Luoyang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao-Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology","place":["Luoyang, Henan, China"]},{"name":"Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases","place":["Luoyang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao-Wan","family":"Chen","sequence":"additional","affiliation":[{"name":"The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, Henan, China"]},{"name":"Luoyang Key Laboratory of Transplantation and Immunological Studies for Haematological Diseases, Department of Clinical Laboratory, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology","place":["Luoyang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"San-Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"The Molecular Medicine Key Laboratory of Liver Injury and Repair, College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology","place":["Luoyang, Henan, China"]},{"name":"Henan Center for Engineering and Technology Research on Prevention and Treatment of Liver Diseases","place":["Luoyang, Henan, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"2259","DOI":"10.1158\/0008-5472.Can-07-5544","article-title":"The role of amphiregulin in exemestane-resistant breast cancer cells: 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