Adipose-derived small extracellular vesicle miR-146a-5p targets Fbx32 to regulate mitochondrial autophagy and delay aging in skeletal muscle
Abstract This study investigates how miR-146a-5p, found in adipose tissue-derived small extracellular vesicles (sEV), influences mitochondrial autophagy and its impact on delaying skeletal muscle aging through the targeting of Fbx32. The findings highlight miR-146a-5p as crucial in skeletal muscle d...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-04-01
|
| Series: | Journal of Nanobiotechnology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12951-025-03367-1 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850184411262222336 |
|---|---|
| author | Mengran Qin Yan Wang Zihan Wang Benchao Dong Peichuan Yang Youyi Liu Qianyun Xi Jianxiong Ma |
| author_facet | Mengran Qin Yan Wang Zihan Wang Benchao Dong Peichuan Yang Youyi Liu Qianyun Xi Jianxiong Ma |
| author_sort | Mengran Qin |
| collection | DOAJ |
| description | Abstract This study investigates how miR-146a-5p, found in adipose tissue-derived small extracellular vesicles (sEV), influences mitochondrial autophagy and its impact on delaying skeletal muscle aging through the targeting of Fbx32. The findings highlight miR-146a-5p as crucial in skeletal muscle development and aging, influencing autophagy, apoptosis, differentiation, and proliferation, collectively impacting muscle atrophy. In C2C12 cells, miR-146a-5p mimics decreased apoptosis, autophagy, and reactive oxygen species (ROS) levels, while enhancing ATP production; conversely, miR-146a-5p inhibitors had the opposite effects. Furthermore, miR-146a-5p-enriched sEV from adipose tissue alleviated skeletal muscle atrophy in aged mice and promoted muscle fiber growth and repair by regulating mitochondrial autophagy and apoptosis. Mechanistically, miR-146a-5p modulated mitochondrial autophagy in myoblasts by targeting Fbx32 and impacting the FoxO3 signaling pathway. This led to a notable decrease in apoptosis-related gene expression, reduced ROS production, and elevated ATP levels. In conclusion, miR-146a-5p derived from WAT-sEV modulates myoblast autophagy, apoptosis, ROS, and differentiation through the Fbx32/FoxO3 signaling axis. This work presents a novel molecular target and theoretical framework for delaying skeletal muscle aging and developing therapies for skeletal muscle-related disorders. |
| format | Article |
| id | doaj-art-5bfa7dcd84da49c8a0ddd3d9bc7fcdb3 |
| institution | OA Journals |
| issn | 1477-3155 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Nanobiotechnology |
| spelling | doaj-art-5bfa7dcd84da49c8a0ddd3d9bc7fcdb32025-08-20T02:17:04ZengBMCJournal of Nanobiotechnology1477-31552025-04-0123111810.1186/s12951-025-03367-1Adipose-derived small extracellular vesicle miR-146a-5p targets Fbx32 to regulate mitochondrial autophagy and delay aging in skeletal muscleMengran Qin0Yan Wang1Zihan Wang2Benchao Dong3Peichuan Yang4Youyi Liu5Qianyun Xi6Jianxiong Ma7Tianjin Hospital, Tianjin UniversityTianjin Hospital, Tianjin UniversityTianjin Key Laboratory of Agricultural Animal Breeding and Healthy Husbandry, College of Animal Science and Veterinary Medicine, Tianjin Agricultural UniversityTianjin Hospital, Tianjin UniversityTianjin Hospital, Tianjin UniversityTianjin Hospital, Tianjin UniversityCollege of Animal Science, Guangdong Province Key Laboratory of Animal Nutritional Regulation, National Engineering Research Center for Breeding Swine Industry, State Key Laboratory of Livestock and Poultry Breeding, South China Agricultural UniversityTianjin Hospital, Tianjin UniversityAbstract This study investigates how miR-146a-5p, found in adipose tissue-derived small extracellular vesicles (sEV), influences mitochondrial autophagy and its impact on delaying skeletal muscle aging through the targeting of Fbx32. The findings highlight miR-146a-5p as crucial in skeletal muscle development and aging, influencing autophagy, apoptosis, differentiation, and proliferation, collectively impacting muscle atrophy. In C2C12 cells, miR-146a-5p mimics decreased apoptosis, autophagy, and reactive oxygen species (ROS) levels, while enhancing ATP production; conversely, miR-146a-5p inhibitors had the opposite effects. Furthermore, miR-146a-5p-enriched sEV from adipose tissue alleviated skeletal muscle atrophy in aged mice and promoted muscle fiber growth and repair by regulating mitochondrial autophagy and apoptosis. Mechanistically, miR-146a-5p modulated mitochondrial autophagy in myoblasts by targeting Fbx32 and impacting the FoxO3 signaling pathway. This led to a notable decrease in apoptosis-related gene expression, reduced ROS production, and elevated ATP levels. In conclusion, miR-146a-5p derived from WAT-sEV modulates myoblast autophagy, apoptosis, ROS, and differentiation through the Fbx32/FoxO3 signaling axis. This work presents a novel molecular target and theoretical framework for delaying skeletal muscle aging and developing therapies for skeletal muscle-related disorders.https://doi.org/10.1186/s12951-025-03367-1sEVmiR-146a-5pFbx32Mitochondrial autophagyAging |
| spellingShingle | Mengran Qin Yan Wang Zihan Wang Benchao Dong Peichuan Yang Youyi Liu Qianyun Xi Jianxiong Ma Adipose-derived small extracellular vesicle miR-146a-5p targets Fbx32 to regulate mitochondrial autophagy and delay aging in skeletal muscle Journal of Nanobiotechnology sEV miR-146a-5p Fbx32 Mitochondrial autophagy Aging |
| title | Adipose-derived small extracellular vesicle miR-146a-5p targets Fbx32 to regulate mitochondrial autophagy and delay aging in skeletal muscle |
| title_full | Adipose-derived small extracellular vesicle miR-146a-5p targets Fbx32 to regulate mitochondrial autophagy and delay aging in skeletal muscle |
| title_fullStr | Adipose-derived small extracellular vesicle miR-146a-5p targets Fbx32 to regulate mitochondrial autophagy and delay aging in skeletal muscle |
| title_full_unstemmed | Adipose-derived small extracellular vesicle miR-146a-5p targets Fbx32 to regulate mitochondrial autophagy and delay aging in skeletal muscle |
| title_short | Adipose-derived small extracellular vesicle miR-146a-5p targets Fbx32 to regulate mitochondrial autophagy and delay aging in skeletal muscle |
| title_sort | adipose derived small extracellular vesicle mir 146a 5p targets fbx32 to regulate mitochondrial autophagy and delay aging in skeletal muscle |
| topic | sEV miR-146a-5p Fbx32 Mitochondrial autophagy Aging |
| url | https://doi.org/10.1186/s12951-025-03367-1 |
| work_keys_str_mv | AT mengranqin adiposederivedsmallextracellularvesiclemir146a5ptargetsfbx32toregulatemitochondrialautophagyanddelayaginginskeletalmuscle AT yanwang adiposederivedsmallextracellularvesiclemir146a5ptargetsfbx32toregulatemitochondrialautophagyanddelayaginginskeletalmuscle AT zihanwang adiposederivedsmallextracellularvesiclemir146a5ptargetsfbx32toregulatemitochondrialautophagyanddelayaginginskeletalmuscle AT benchaodong adiposederivedsmallextracellularvesiclemir146a5ptargetsfbx32toregulatemitochondrialautophagyanddelayaginginskeletalmuscle AT peichuanyang adiposederivedsmallextracellularvesiclemir146a5ptargetsfbx32toregulatemitochondrialautophagyanddelayaginginskeletalmuscle AT youyiliu adiposederivedsmallextracellularvesiclemir146a5ptargetsfbx32toregulatemitochondrialautophagyanddelayaginginskeletalmuscle AT qianyunxi adiposederivedsmallextracellularvesiclemir146a5ptargetsfbx32toregulatemitochondrialautophagyanddelayaginginskeletalmuscle AT jianxiongma adiposederivedsmallextracellularvesiclemir146a5ptargetsfbx32toregulatemitochondrialautophagyanddelayaginginskeletalmuscle |