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

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, ob...

Full description

Saved in:
Bibliographic Details
Main Authors: Feng Hua, Jinpeng Sun, Mohan Shi, Rui Mei, Zeyuan Song, Jun Liu, Mingshun Zhang
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:npj Regenerative Medicine
Online Access:https://doi.org/10.1038/s41536-024-00388-6
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1841559844258054144
author Feng Hua
Jinpeng Sun
Mohan Shi
Rui Mei
Zeyuan Song
Jun Liu
Mingshun Zhang
author_facet Feng Hua
Jinpeng Sun
Mohan Shi
Rui Mei
Zeyuan Song
Jun Liu
Mingshun Zhang
author_sort Feng Hua
collection DOAJ
description 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.
format Article
id doaj-art-d376228edecd4d8fa3ef6bd1d140c2e2
institution Kabale University
issn 2057-3995
language English
publishDate 2024-12-01
publisher Nature Portfolio
record_format Article
series npj Regenerative Medicine
spelling doaj-art-d376228edecd4d8fa3ef6bd1d140c2e22025-01-05T12:10:50ZengNature Portfolionpj Regenerative Medicine2057-39952024-12-019111410.1038/s41536-024-00388-6Macrophage-derived extracellular vesicles transfer mitochondria to adipocytes and promote adipocyte–myofibroblast transition in epidural fibrosisFeng Hua0Jinpeng Sun1Mohan Shi2Rui Mei3Zeyuan Song4Jun Liu5Mingshun Zhang6Department of Orthopedics, The Second Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Nanjing Medical UniversityDepartment of Orthopedics, The Second Affiliated Hospital of Nanjing Medical UniversityNHC Key Laboratory of Antibody Technique, Jiangsu Province Engineering Research Center of Antibody Drug, Department of Immunology, Nanjing Medical UniversityAbstract 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.https://doi.org/10.1038/s41536-024-00388-6
spellingShingle Feng Hua
Jinpeng Sun
Mohan Shi
Rui Mei
Zeyuan Song
Jun Liu
Mingshun Zhang
Macrophage-derived extracellular vesicles transfer mitochondria to adipocytes and promote adipocyte–myofibroblast transition in epidural fibrosis
npj Regenerative Medicine
title Macrophage-derived extracellular vesicles transfer mitochondria to adipocytes and promote adipocyte–myofibroblast transition in epidural fibrosis
title_full Macrophage-derived extracellular vesicles transfer mitochondria to adipocytes and promote adipocyte–myofibroblast transition in epidural fibrosis
title_fullStr Macrophage-derived extracellular vesicles transfer mitochondria to adipocytes and promote adipocyte–myofibroblast transition in epidural fibrosis
title_full_unstemmed Macrophage-derived extracellular vesicles transfer mitochondria to adipocytes and promote adipocyte–myofibroblast transition in epidural fibrosis
title_short Macrophage-derived extracellular vesicles transfer mitochondria to adipocytes and promote adipocyte–myofibroblast transition in epidural fibrosis
title_sort macrophage derived extracellular vesicles transfer mitochondria to adipocytes and promote adipocyte myofibroblast transition in epidural fibrosis
url https://doi.org/10.1038/s41536-024-00388-6
work_keys_str_mv AT fenghua macrophagederivedextracellularvesiclestransfermitochondriatoadipocytesandpromoteadipocytemyofibroblasttransitioninepiduralfibrosis
AT jinpengsun macrophagederivedextracellularvesiclestransfermitochondriatoadipocytesandpromoteadipocytemyofibroblasttransitioninepiduralfibrosis
AT mohanshi macrophagederivedextracellularvesiclestransfermitochondriatoadipocytesandpromoteadipocytemyofibroblasttransitioninepiduralfibrosis
AT ruimei macrophagederivedextracellularvesiclestransfermitochondriatoadipocytesandpromoteadipocytemyofibroblasttransitioninepiduralfibrosis
AT zeyuansong macrophagederivedextracellularvesiclestransfermitochondriatoadipocytesandpromoteadipocytemyofibroblasttransitioninepiduralfibrosis
AT junliu macrophagederivedextracellularvesiclestransfermitochondriatoadipocytesandpromoteadipocytemyofibroblasttransitioninepiduralfibrosis
AT mingshunzhang macrophagederivedextracellularvesiclestransfermitochondriatoadipocytesandpromoteadipocytemyofibroblasttransitioninepiduralfibrosis