Lipid metabolism of apoptotic vesicles accelerates cutaneous wound healing by modulating macrophage function

Abstract The application of apoptotic extracellular vesicles (ApoEVs) derived from stem cell in skin wound healing has garnered significant attention. In recent decades, scholars have shown that extracellular vesicles (EVs) established intercellular communication by carrying proteins or microRNAs, t...

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Main Authors: Yuan Qin, Xin Chen, Lili Bao, Lili Ren, Geng Dou, Jianing Lian, Shujuan Xing, Zihan Li, Feng Ding, Wen Qin, Xulin Liu, Bin Zhu, Shiyu Liu, Zuolin Jin, Xiaoshan Yang
Format: Article
Language:English
Published: BMC 2025-02-01
Series:Journal of Nanobiotechnology
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Online Access:https://doi.org/10.1186/s12951-025-03194-4
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author Yuan Qin
Xin Chen
Lili Bao
Lili Ren
Geng Dou
Jianing Lian
Shujuan Xing
Zihan Li
Feng Ding
Wen Qin
Xulin Liu
Bin Zhu
Shiyu Liu
Zuolin Jin
Xiaoshan Yang
author_facet Yuan Qin
Xin Chen
Lili Bao
Lili Ren
Geng Dou
Jianing Lian
Shujuan Xing
Zihan Li
Feng Ding
Wen Qin
Xulin Liu
Bin Zhu
Shiyu Liu
Zuolin Jin
Xiaoshan Yang
author_sort Yuan Qin
collection DOAJ
description Abstract The application of apoptotic extracellular vesicles (ApoEVs) derived from stem cell in skin wound healing has garnered significant attention. In recent decades, scholars have shown that extracellular vesicles (EVs) established intercellular communication by carrying proteins or microRNAs, the role of lipids in EVs in wound healing has yet to be clarified. Here, we focus on the key role of group X secretory phospholipase A2 (sPLA2-X) in lipid metabolism. Specifically, sPLA2-X significantly increased the production of the anti-inflammatory lipid mediators, resolvin D5 (RvD5), by hydrolyzing phospholipids in ApoEVs. This change not only promoted the uptake of ApoEVs by macrophages, but also effectively inhibited the expression of tumor necrosis factor-alpha (TNF-α) in macrophages, promoting the healing of skin wounds. In summary, this study contributes to our understanding of the mechanisms by which ApoEVs support skin defect repair and offers a potential theoretical approach for using ApoEVs in skin wound treatment. With further research and optimization, it is expected that more efficient and secure ApoEVs-based treatment strategies will be developed, bringing new breakthroughs in clinical treatment of skin injuries and related diseases. Graphical abstract
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spelling doaj-art-5366756def1d4a8da600637a568e9f1f2025-08-20T02:48:22ZengBMCJournal of Nanobiotechnology1477-31552025-02-0123111510.1186/s12951-025-03194-4Lipid metabolism of apoptotic vesicles accelerates cutaneous wound healing by modulating macrophage functionYuan Qin0Xin Chen1Lili Bao2Lili Ren3Geng Dou4Jianing Lian5Shujuan Xing6Zihan Li7Feng Ding8Wen Qin9Xulin Liu10Bin Zhu11Shiyu Liu12Zuolin Jin13Xiaoshan Yang14State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology & Clinic of Oral Rare Diseases and Genetic Disease, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology & Clinic of Oral Rare Diseases and Genetic Disease, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityCollege of Pharmacy, Shaanxi University of Chinese MedicineState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi International Joint Research Center for Oral Diseases, Center for Tissue Engineering, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical UniversityOutpatient Department, General Hospital of Xizang Military RegionState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology & Clinic of Oral Rare Diseases and Genetic Disease, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Orthodontics, School of Stomatology, The Fourth Military Medical UniversityState Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Key Laboratory of Stomatology, Department of Oral Biology & Clinic of Oral Rare Diseases and Genetic Disease, School of Stomatology, The Fourth Military Medical UniversityAbstract The application of apoptotic extracellular vesicles (ApoEVs) derived from stem cell in skin wound healing has garnered significant attention. In recent decades, scholars have shown that extracellular vesicles (EVs) established intercellular communication by carrying proteins or microRNAs, the role of lipids in EVs in wound healing has yet to be clarified. Here, we focus on the key role of group X secretory phospholipase A2 (sPLA2-X) in lipid metabolism. Specifically, sPLA2-X significantly increased the production of the anti-inflammatory lipid mediators, resolvin D5 (RvD5), by hydrolyzing phospholipids in ApoEVs. This change not only promoted the uptake of ApoEVs by macrophages, but also effectively inhibited the expression of tumor necrosis factor-alpha (TNF-α) in macrophages, promoting the healing of skin wounds. In summary, this study contributes to our understanding of the mechanisms by which ApoEVs support skin defect repair and offers a potential theoretical approach for using ApoEVs in skin wound treatment. With further research and optimization, it is expected that more efficient and secure ApoEVs-based treatment strategies will be developed, bringing new breakthroughs in clinical treatment of skin injuries and related diseases. Graphical abstracthttps://doi.org/10.1186/s12951-025-03194-4ApoEVsLipid mediatorsSkin wound healingsPLA2-XRvD5
spellingShingle Yuan Qin
Xin Chen
Lili Bao
Lili Ren
Geng Dou
Jianing Lian
Shujuan Xing
Zihan Li
Feng Ding
Wen Qin
Xulin Liu
Bin Zhu
Shiyu Liu
Zuolin Jin
Xiaoshan Yang
Lipid metabolism of apoptotic vesicles accelerates cutaneous wound healing by modulating macrophage function
Journal of Nanobiotechnology
ApoEVs
Lipid mediators
Skin wound healing
sPLA2-X
RvD5
title Lipid metabolism of apoptotic vesicles accelerates cutaneous wound healing by modulating macrophage function
title_full Lipid metabolism of apoptotic vesicles accelerates cutaneous wound healing by modulating macrophage function
title_fullStr Lipid metabolism of apoptotic vesicles accelerates cutaneous wound healing by modulating macrophage function
title_full_unstemmed Lipid metabolism of apoptotic vesicles accelerates cutaneous wound healing by modulating macrophage function
title_short Lipid metabolism of apoptotic vesicles accelerates cutaneous wound healing by modulating macrophage function
title_sort lipid metabolism of apoptotic vesicles accelerates cutaneous wound healing by modulating macrophage function
topic ApoEVs
Lipid mediators
Skin wound healing
sPLA2-X
RvD5
url https://doi.org/10.1186/s12951-025-03194-4
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