REVIEW article

Front. Immunol.

Sec. Inflammation

Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1583616

This article is part of the Research TopicThe Role of TGF-beta Superfamily Members in Immune Homeostasis and DiseaseView all 7 articles

TGF-β Inhibitors: the Future for Prevention and Treatment of Liver Fibrosis?

Provisionally accepted
Weili WangWeili Wang1Yilin GaoYilin Gao1Yizhen ChenYizhen Chen1Meng ChengMeng Cheng2Yonghao SangYonghao Sang1Liuting WeiLiuting Wei1Rong DaiRong Dai2Yiping WangYiping Wang2Lei ZhangLei Zhang2*
  • 1First Clinical Medical College, Anhui University of Chinese Medicine, Hefei, China., Hefei, China
  • 2First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China

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Liver fibrosis is a core pathological process in the progression of chronic liver diseases to cirrhosis and hepatocellular carcinoma, characterized by abnormal deposition of extracellular matrix. Transforming growth factor-β (TGF-β), through classical small mothers against decapentaplegic (Smad)-dependent and non-Smad-dependent pathways, activates hepatic stellate cells to transdifferentiate into myofibroblasts, promotes extracellular matrix synthesis, and regulates immunity, serving as a key driver of fibrogenesis. This review systematically summarizes the role of TGF-β in liver fibrosis and details the research progress of TGF-β-targeted inhibitors. Studies show that TGF-β neutralizing antibodies, small molecule receptor antagonists, small molecule signaling inhibitors, and natural compounds and extracts significantly improve experimental liver fibrosis by inhibiting Smad or non-Smad pathways. In clinical trials, drugs such as Pirfenidone and Hydronidone have demonstrated potential for fibrosis reversal in patients with chronic hepatitis. Although TGF-β-targeted therapy has made breakthroughs in basic research and clinical translation, future studies need to focus on multitarget drug design, personalized treatment regimens, and novel delivery systems to accelerate the transition from preclinical research to clinical application, providing innovative therapeutic strategies for liver fibrosis and related liver diseases.

Keywords: liver fibrosis, TGF-β signaling pathway, TGF-β inhibitors, Hepatic Stellate Cells, Antifibrotic therapy

Received: 26 Feb 2025; Accepted: 03 Jun 2025.

Copyright: © 2025 Wang, Gao, Chen, Cheng, Sang, Wei, Dai, Wang and Zhang. 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: Lei Zhang, First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, China

Disclaimer: 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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