RETRACTED: Nestin Regulates Autophagy‐Dependent Ferroptosis Mediated Skeletal Muscle Atrophy by Ubiquitinating MAP 1LC3B

作者：Shunshun Han, Xiyu Zhao, Chunlin Yu, Can Cui, Yao Zhang, Qing Zhu, Mohan Qiu, Chaowu Yang, Huadong Yin · 发表于：Journal of Cachexia Sarcopenia and Muscle · 年份：2025 · DOI：10.1002/jcsm.13779 · 被引用次数：13 · 研究领域：Muscle Physiology and Disorders、Ferroptosis and cancer prognosis、Nutrition and Health in Aging

ABSTRACT Background Programmed cell death plays a critical role in skeletal muscle atrophy. Ferroptosis, an iron‐dependent form of programmed cell death driven by lipid peroxidation, has been implicated in various diseases, but its role in skeletal muscle atrophy remains unclear. Methods Ferroptosis in skeletal muscle atrophy was investigated using two models: dexamethasone (Dex)‐induced atrophy ( n = 6 independent cell cultures per group) and simulated microgravity ( n = 6 mice per group). Conditional Nestin knockout (KO) mice were generated using CRISPR/Cas9 ( n = 6–8 mice per group), with wild‐type (WT) controls ( n = 6–8). Phenotypic analyses included histopathology (HE staining), functional assessments (muscle strength, weight analysis, treadmill), and dystrophy evaluation (dystrophin staining). Molecular analyses involved flow cytometry, ELISA, transmission electron microscopy, PI staining, and IP/MS to delineate Nestin‐regulated ferroptosis pathways in skeletal muscle atrophy. Results Ferroptosis was significantly activated in both atrophy models, with a 2.5‐fold increase in lipid peroxidation ( p < 0.01), a 2‐fold accumulation of Fe 2+ ( p < 0.01) and a 50% reduction in Nestin expression ( p < 0.001). Nestin KO mice exhibited exacerbated muscle atrophy, showing a 40% decrease in muscle weight ( p < 0.01) and a 30% reduction in muscle strength ( p < 0.05) compared to WT mice. Nestin overexpression mitigated Dex‐induced ferroptosis, reducing lipid peroxid...