Adipose-derived small extracellular vesicle miR-146a-5p targets Fbx32 to regulate mitochondrial autophagy and delay aging in skeletal muscle

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...

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Bibliographic Details
Main Authors: Mengran Qin, Yan Wang, Zihan Wang, Benchao Dong, Peichuan Yang, Youyi Liu, Qianyun Xi, Jianxiong Ma
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Journal of Nanobiotechnology
Subjects:
sEV
miR-146a-5p
Fbx32
Mitochondrial autophagy
Aging
Online Access:https://doi.org/10.1186/s12951-025-03367-1
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Summary: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.
ISSN:1477-3155

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