REVIEW article
Front. Cell Dev. Biol.
Sec. Signaling
Fibroblast PI3K/AKT Signaling and Extracellular Matrix Homeostasis: Mechanisms, Targets, and Delivery Challenges
Provisionally accepted
- 1First Affiliated Hospital of Gannan Medical University, Nanchang, China
- 2Gannan Medical University, Ganzhou, China
- 3Wan'an County People's Hospital, Wan'an, China
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The extracellular matrix (ECM) is essential for tissue homeostasis, ensuring structural stability, facilitating cell-cell communication, and tightly controlling key cellular processes, including proliferation, differentiation, and migration. Numerous cell types and signalling cascades direct ECM turnover; chief among them, the phosphatidyl-inositol-3-kinase (PI3K)/AKT (protein kinase B, PKB) axis remains intensively studied in fibroblasts. Recent evidence indicates that the integration of extracellular cues with intracellular mediators in fibroblasts can modulate the impact of the PI3K/AKT pathway on the ECM. This process is intricately linked to critical fibroblast functions such as metabolic reprogramming, autophagy, apoptosis, and stress responses, ultimately shaping outcomes in fibrotic diseases, wound healing, tissue remodelling, and pathological scar formation. Whereas conventional reviews centre on site-restricted subsets in single disorders, we integrate multi-tissue insights to chart PI3K/AKT signalling across heterogeneous fibroblast populations, taxonomising their sources into a unifying framework that confronts heterogeneity and accelerates precision therapeutic design.
Keywords: cell therapy, Extracellular Matrix, fibroblast, PI3K/AKT, targeted therapy
Received: 08 Aug 2025; Accepted: 01 Dec 2025.
Copyright: © 2025 Fang, Zeng, Ni, Wen, Fang, Zou 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: Guoxi Zhang
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