Biomolecules, Vol. 15, Pages 1072: Glucocorticoid-Induced Muscle Satellite Cell-Derived Extracellular Vesicles Mediate Skeletal Muscle Atrophy via the miR-335-5p/MAPK11/iNOS Pathway

Biomolecules doi: 10.3390/biom15081072

Authors:
Pei Ma
Jiarui Wu
Ruiyuan Zhou
Linli Xue
Xiaomao Luo
Yi Yan
Jiayin Lu
Yanjun Dong
Jianjun Geng
Haidong Wang

Prolonged high-dose administration of synthetic glucocorticoids (GCs) leads to limb muscle atrophy and weakness, yet its underlying mechanisms remain incompletely understood. Muscle fibers and muscle satellite cells (MSCs) are essential for skeletal muscle development and associated pathologies. This study demonstrates that dexamethasone (Dex) induced MSC-derived extracellular vesicles (EVs) impair myogenesis in muscle fiber-like cells (MFLCs) via inducible nitric oxide synthase (iNOS) suppression. High-throughput sequencing revealed a marked upregulation of miR-335-5p in MSC-derived EVs following Dex treatment. Mechanistically, EV miR-335-5p targeted MAPK11, leading to iNOS downregulation and subsequent UPS activation in MFLCs, which directly promoted muscle protein degradation. Collectively, our findings identify the EV miR-335-5p/MAPK11/iNOS axis as a critical mediator of GC-induced muscle atrophy, offering novel insights into therapeutic strategies targeting EV-mediated signaling in muscle wasting disorders.

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Pei Ma www.mdpi.com