REVIEW article
Front. Oncol.
Sec. Molecular and Cellular Oncology
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1649179
The Pivotal Role of TGF-β/Smad Pathway in Fibrosis Pathogenesis and Treatment
Provisionally accepted
- 1Chengdu Sport University, Chengdu, China
- 2Jinfeng Laboratory, Chongqing, China
- 3Army Medical University, Chongqing, China
- 4Southwest Medical University, Luzhou, China
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Fibrosis, which is characterized by pathological extracellular matrix (ECM) accumulation impairing organ function, is governed primarily by dysregulated transforming growth factor-β (TGF-β)/Smad signalling. TGF-β1 triggers canonical (Smad2/3-dependent) and noncanonical pathways upon receptor binding, driving profibrotic processes such as fibroblast activation, epithelial-mesenchymal transition (EMT), excessive ECM production (e.g., collagen), and the suppression of matrix degradation. This pathway is central to organ-specific fibrogenesis: In liver fibrosis, it activates hepatic stellate cells (HSCs); in renal fibrosis, it promotes tubular injury and ECM deposition; in pulmonary fibrosis, it induces EMT/fibroblast transition in radiation/bleomycin models; in cardiac fibrosis, it mediates fibroblast activation in diabetic cardiomyopathy/atrial fibrillation via NPRC/TGIF1/USP mechanisms; and in skin fibrosis (e.g., scleroderma), it stimulates collagen overproduction, which is suppressed by osthole or mesenchymal stem cells. The TGF-β/Smad axis thus represents a pivotal therapeutic target. Future research should clarify tissue-specific regulatory networks and develop combinatorial antifibrotic strategies.
Keywords: Fibrosis, TGF-β/Smad signalling pathway, ECM, miRNA, EMT
Received: 18 Jun 2025; Accepted: 18 Aug 2025.
Copyright: © 2025 Chen, Lyu, Xing, Chen, Hu, Wang and Ai. 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: Feilong Chen, Chengdu Sport University, Chengdu, China
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