REVIEW article
Front. Pharmacol.
Sec. Integrative and Regenerative Pharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1678953
The PI3K/AKT/mTOR Pathway in Scar Remodeling and Keloid Formation: Mechanisms and Therapeutic Perspectives
Provisionally accepted
- Shijiazhuang People’s Hospital, Shijiazhuang, China
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Keloids and hypertrophic scars (HTS) represent aberrant wound healing characterized by excessive fibroblast activity and extracellular matrix accumulation. The PI3K/AKT/mTOR signaling pathway is vital in regulating these processes, promoting fibroblast proliferation, survival, and collagen synthesis. Dysregulation of this pathway, driven by genetic mutations, post-transcriptional modulation, and upstream signaling, contributes significantly to the pathogenesis of pathological scarring. This review collects current knowledge on the molecular mechanisms underlying PI3K/AKT/mTOR activation in keloids and HTS, highlighting the roles of key regulators such as PTEN, NEDD4, and non-coding RNAs. It also evaluates therapeutic strategies targeting this axis, including small-molecule inhibitors, natural compounds, and emerging delivery platforms. Targeting PI3K/AKT/mTOR offers a compelling avenue for developing effective, mechanism-based keloid and hypertrophic scarring treatments. The PI3K/AKT/mTOR signaling axis is central to these cellular mechanisms, which drive fibroblast proliferation, survival, myofibroblast transdifferentiation, and metabolic reprogramming (including suppressed autophagy and enhanced glycolysis.
Keywords: Keloid, hypertrophic scar, PI3K/Akt/mTOR pathway, Fibroblast proliferation, Extracellular Matrix, non-coding RNAs, targeted therapy, Drug delivery platforms
Received: 03 Aug 2025; Accepted: 15 Oct 2025.
Copyright: © 2025 Liu, Yan, Qi, Zhang, Zhang and Zhao. 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: Yaping Zhao, yapingzhao893@gmail.com
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