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巨噬细胞衍生的细胞外囊泡将线粒体转移至脂肪细胞，并促进硬膜外纤维化中脂肪细胞向肌成纤维细胞的转变。

Macrophage-derived extracellular vesicles transfer mitochondria to adipocytes and promote adipocyte-myofibroblast transition in epidural fibrosis.

作者信息

Hua Feng, Sun Jinpeng, Shi Mohan, Mei Rui, Song Zeyuan, Liu Jun, Zhang Mingshun

机构信息

Department of Orthopedics, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

NHC Key Laboratory of Antibody Technique, Jiangsu Province Engineering Research Center of Antibody Drug, Department of Immunology, Nanjing Medical University, Nanjing, China.

出版信息

NPJ Regen Med. 2024 Dec 30;9(1):43. doi: 10.1038/s41536-024-00388-6.

DOI:10.1038/s41536-024-00388-6
PMID:39738050
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11685489/
Abstract

Epidural fibrosis post laminectomy is the leading cause of failed back surgery syndrome. Little is known about the role and mechanisms of adipose tissues in epidural fibrosis. Here, we found that obese patients were more likely to develop epidural fibrosis after spine surgery. Similarly, obesity led to more progressive epidural fibrosis in a mouse model of laminectomy. Adipocyte-myofibroblast transition (AMT) occurs in epidural scarring. Mechanistically, large extracellular vesicles (EVs) from M2-type macrophages transfer mitochondria into adipocytes and promote AMT by activating the TGF-β and PAI-1 pathways. Blocking the PAI-1 pathway significantly attenuated the transition of adipocytes into myofibroblasts. We conclude that large EVs from macrophages transfer mitochondria to promote AMT in epidural fibrosis.

摘要

椎板切除术后硬膜外纤维化是腰椎手术失败综合征的主要原因。目前对于脂肪组织在硬膜外纤维化中的作用和机制知之甚少。在此，我们发现肥胖患者在脊柱手术后更易发生硬膜外纤维化。同样，在椎板切除小鼠模型中，肥胖导致更严重的进行性硬膜外纤维化。脂肪细胞-肌成纤维细胞转分化（AMT）发生于硬膜外瘢痕形成过程中。机制上，M2型巨噬细胞来源的大型细胞外囊泡（EVs）将线粒体转移至脂肪细胞，并通过激活TGF-β和PAI-1信号通路促进AMT。阻断PAI-1信号通路可显著减弱脂肪细胞向肌成纤维细胞的转分化。我们得出结论，巨噬细胞来源的大型EVs通过转移线粒体促进硬膜外纤维化中的AMT。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/1126186169a4/41536_2024_388_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/cd9249e26f07/41536_2024_388_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/2c8f74603a1a/41536_2024_388_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/bdf6330b04e4/41536_2024_388_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/74776d2a04d0/41536_2024_388_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/ecc979fc02d5/41536_2024_388_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/d177c3f3c4cc/41536_2024_388_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/1126186169a4/41536_2024_388_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/cd9249e26f07/41536_2024_388_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/2c8f74603a1a/41536_2024_388_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/bdf6330b04e4/41536_2024_388_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/74776d2a04d0/41536_2024_388_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/ecc979fc02d5/41536_2024_388_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/d177c3f3c4cc/41536_2024_388_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d074/11685489/1126186169a4/41536_2024_388_Fig7_HTML.jpg

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[1]
Macrophage-derived extracellular vesicles transfer mitochondria to adipocytes and promote adipocyte-myofibroblast transition in epidural fibrosis.

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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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引用本文的文献

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Front Cell Infect Microbiol. 2025-8-11

[2]
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本文引用的文献

[1]
Myeloid-derived miR-6236 potentiates adipocyte insulin signaling and prevents hyperglycemia during obesity.

Nat Commun. 2024-6-25

[2]
Serpin E1 mediates the induction of renal tubular degeneration and premature senescence upon diabetic insult.

Sci Rep. 2023-9-27

[3]
Mitochondria are secreted in extracellular vesicles when lysosomal function is impaired.

Nat Commun. 2023-8-18

[4]
Tumor-associated macrophages trigger MAIT cell dysfunction at the HCC invasive margin.

Cell. 2023-8-17

[5]
GIP receptor agonism improves dyslipidemia and atherosclerosis independently of body weight loss in preclinical mouse model for cardio-metabolic disease.

Cardiovasc Diabetol. 2023-8-17

[6]
White adipose tissue mitochondrial bioenergetics in metabolic diseases.

Rev Endocr Metab Disord. 2023-12

[7]
M1/M2 macrophages and their overlaps - myth or reality?

Clin Sci (Lond). 2023-8-14

[8]
Iron induces B cell pyroptosis through Tom20-Bax-caspase-gasdermin E signaling to promote inflammation post-spinal cord injury.

J Neuroinflammation. 2023-7-22

[9]
Mitochondria-derived cell-to-cell communication.

Cell Rep. 2023-7-25

[10]
Wound infiltrating adipocytes are not myofibroblasts.

Nat Commun. 2023-5-25

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