miRNA-125b-5p-rich exosomes derived from fibro-adipogenic progenitors promoting muscle regeneration through inducing pro-regenerative macrophages

Abstract It is still unclear the role of exosomes derived from fibro-adipogenic progenitors (FAP) on macrophage polarization and muscle repair. In this study, the effects of exosomes collected from primary FAPs isolated from acute injured muscles at different timepoints on macrophage polarization we...

Full description

Saved in:
Bibliographic Details
Main Authors: Meng-meng Yang, Jing-ya Luo, Jia Cai, Jin Qian, Xiao-yan Zhu, Hui-zhen Zou, Gao-ming Li, Jing Dai, Huang Zhu, Wei Li, Li-dan Zhang, Xia Kang
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Stem Cell Research & Therapy
Online Access:https://doi.org/10.1186/s13287-025-04452-w
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849333142857449472
author Meng-meng Yang
Jing-ya Luo
Jia Cai
Jin Qian
Xiao-yan Zhu
Hui-zhen Zou
Gao-ming Li
Jing Dai
Huang Zhu
Wei Li
Li-dan Zhang
Xia Kang
author_facet Meng-meng Yang
Jing-ya Luo
Jia Cai
Jin Qian
Xiao-yan Zhu
Hui-zhen Zou
Gao-ming Li
Jing Dai
Huang Zhu
Wei Li
Li-dan Zhang
Xia Kang
author_sort Meng-meng Yang
collection DOAJ
description Abstract It is still unclear the role of exosomes derived from fibro-adipogenic progenitors (FAP) on macrophage polarization and muscle repair. In this study, the effects of exosomes collected from primary FAPs isolated from acute injured muscles at different timepoints on macrophage polarization were compared. We found exosomes derived from FAPs isolated at 10 (days post injury, DPI) can effectively induce M2 macrophage polarization both in vitro and in vivo. In addition, the pro-regenerative capacity of macrophages can be enhanced to support the activation of MuSCs and muscle repair. As we confirmed that RNAs played an important role in mediating the function of FAPD10-exos on inducing M2 macrophage polarization, using miRNA sequencing, miR-125b-5p was screened and confirmed as the key regulator to induce M2 macrophage polarization through targeting PTPN1. Furthermore, miR-125b-5p inhibited the activation of ERK pathway through inhibiting the expression of PTPN1. Overall, FAPD10-exos as well as miR-125b-5p exerted a nano-therapeutical function for muscle repair.
format Article
id doaj-art-d900c973a04a4cb1b91c1ed66dc088b5
institution Kabale University
issn 1757-6512
language English
publishDate 2025-07-01
publisher BMC
record_format Article
series Stem Cell Research & Therapy
spelling doaj-art-d900c973a04a4cb1b91c1ed66dc088b52025-08-20T03:45:57ZengBMCStem Cell Research & Therapy1757-65122025-07-0116111610.1186/s13287-025-04452-wmiRNA-125b-5p-rich exosomes derived from fibro-adipogenic progenitors promoting muscle regeneration through inducing pro-regenerative macrophagesMeng-meng Yang0Jing-ya Luo1Jia Cai2Jin Qian3Xiao-yan Zhu4Hui-zhen Zou5Gao-ming Li6Jing Dai7Huang Zhu8Wei Li9Li-dan Zhang10Xia Kang11Center for Medical Epigenetics, School of Basic Medical Sciences, Chongqing Medical UniversityPancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater CommandLaboratory of Basic Medicine, The General Hospital of Western Theater CommandPancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater CommandLaboratory of Basic Medicine, The General Hospital of Western Theater CommandPancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater CommandDisease Surveillance Division, Center for Disease Control and Prevention of the Central Theater CommandPancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater CommandHyperbaric Oxygen Therapy Center, The General Hospital of Western Theater CommandPancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater CommandCenter for Medical Epigenetics, School of Basic Medical Sciences, Chongqing Medical UniversityPancreatic Injury and Repair Key Laboratory of Sichuan Province, The General Hospital of Western Theater CommandAbstract It is still unclear the role of exosomes derived from fibro-adipogenic progenitors (FAP) on macrophage polarization and muscle repair. In this study, the effects of exosomes collected from primary FAPs isolated from acute injured muscles at different timepoints on macrophage polarization were compared. We found exosomes derived from FAPs isolated at 10 (days post injury, DPI) can effectively induce M2 macrophage polarization both in vitro and in vivo. In addition, the pro-regenerative capacity of macrophages can be enhanced to support the activation of MuSCs and muscle repair. As we confirmed that RNAs played an important role in mediating the function of FAPD10-exos on inducing M2 macrophage polarization, using miRNA sequencing, miR-125b-5p was screened and confirmed as the key regulator to induce M2 macrophage polarization through targeting PTPN1. Furthermore, miR-125b-5p inhibited the activation of ERK pathway through inhibiting the expression of PTPN1. Overall, FAPD10-exos as well as miR-125b-5p exerted a nano-therapeutical function for muscle repair.https://doi.org/10.1186/s13287-025-04452-w
spellingShingle Meng-meng Yang
Jing-ya Luo
Jia Cai
Jin Qian
Xiao-yan Zhu
Hui-zhen Zou
Gao-ming Li
Jing Dai
Huang Zhu
Wei Li
Li-dan Zhang
Xia Kang
miRNA-125b-5p-rich exosomes derived from fibro-adipogenic progenitors promoting muscle regeneration through inducing pro-regenerative macrophages
Stem Cell Research & Therapy
title miRNA-125b-5p-rich exosomes derived from fibro-adipogenic progenitors promoting muscle regeneration through inducing pro-regenerative macrophages
title_full miRNA-125b-5p-rich exosomes derived from fibro-adipogenic progenitors promoting muscle regeneration through inducing pro-regenerative macrophages
title_fullStr miRNA-125b-5p-rich exosomes derived from fibro-adipogenic progenitors promoting muscle regeneration through inducing pro-regenerative macrophages
title_full_unstemmed miRNA-125b-5p-rich exosomes derived from fibro-adipogenic progenitors promoting muscle regeneration through inducing pro-regenerative macrophages
title_short miRNA-125b-5p-rich exosomes derived from fibro-adipogenic progenitors promoting muscle regeneration through inducing pro-regenerative macrophages
title_sort mirna 125b 5p rich exosomes derived from fibro adipogenic progenitors promoting muscle regeneration through inducing pro regenerative macrophages
url https://doi.org/10.1186/s13287-025-04452-w
work_keys_str_mv AT mengmengyang mirna125b5prichexosomesderivedfromfibroadipogenicprogenitorspromotingmuscleregenerationthroughinducingproregenerativemacrophages
AT jingyaluo mirna125b5prichexosomesderivedfromfibroadipogenicprogenitorspromotingmuscleregenerationthroughinducingproregenerativemacrophages
AT jiacai mirna125b5prichexosomesderivedfromfibroadipogenicprogenitorspromotingmuscleregenerationthroughinducingproregenerativemacrophages
AT jinqian mirna125b5prichexosomesderivedfromfibroadipogenicprogenitorspromotingmuscleregenerationthroughinducingproregenerativemacrophages
AT xiaoyanzhu mirna125b5prichexosomesderivedfromfibroadipogenicprogenitorspromotingmuscleregenerationthroughinducingproregenerativemacrophages
AT huizhenzou mirna125b5prichexosomesderivedfromfibroadipogenicprogenitorspromotingmuscleregenerationthroughinducingproregenerativemacrophages
AT gaomingli mirna125b5prichexosomesderivedfromfibroadipogenicprogenitorspromotingmuscleregenerationthroughinducingproregenerativemacrophages
AT jingdai mirna125b5prichexosomesderivedfromfibroadipogenicprogenitorspromotingmuscleregenerationthroughinducingproregenerativemacrophages
AT huangzhu mirna125b5prichexosomesderivedfromfibroadipogenicprogenitorspromotingmuscleregenerationthroughinducingproregenerativemacrophages
AT weili mirna125b5prichexosomesderivedfromfibroadipogenicprogenitorspromotingmuscleregenerationthroughinducingproregenerativemacrophages
AT lidanzhang mirna125b5prichexosomesderivedfromfibroadipogenicprogenitorspromotingmuscleregenerationthroughinducingproregenerativemacrophages
AT xiakang mirna125b5prichexosomesderivedfromfibroadipogenicprogenitorspromotingmuscleregenerationthroughinducingproregenerativemacrophages