Engineered Muscle Tissue Analysis of Irisin Protection Against Glucocorticoid- and Cancer Cachexia-Induced Muscle Wasting and Cardiotoxicity

作者：Son YH, Sheng CY, Jeong JE, Choi Y, Jung H, Won J, Atinsky A, Park J, Kim JC, Lee KY, Park YI, Park SJ · 发表于：Biochip journal · 年份：2026 · DOI：10.1007/s13206-026-00268-9 · 被引用次数：66

UNLABELLED: Muscle atrophy, a condition characterized by an imbalance between protein synthesis and degradation, leads to skeletal muscle wasting, exacerbating disease progression and increasing mortality rates. Exercise has been shown to counteract muscle wasting, with myokines-exercise-induced secretome proteins, and among them, irisin is known to mediate systemic benefits such as improved metabolism, reduction of oxidative stress, and promotion of tissue repair in skeletal muscle, thereby mediating beneficial effects of exercise against atrophy. Despite its promising therapeutic potential, the precise functions and signaling pathways of irisin in muscle and other organs remain insufficiently explored owing to the complexity and heterogeneity of in vivo environments. In this study, we present engineered skeletal muscle tissue models as biomimetic platforms to study irisin-mediated therapeutic interventions. Using this platform, we validated the ability of irisin to mitigate dexamethasone (DEX)-induced muscle atrophy by restoring myogenic markers, enhancing AKT-mediated protein synthesis, suppressing ubiquitin-proteasome-driven degradation, and preserving contractile function under catabolic stress. (e.g., irisin pretreatment increased tetanic stress in DEX-treated tissues by ~ 43% vs. DEX alone, n = 7-9 per group, p < 0.05). Furthermore, irisin effectively counteracted cancer cachexia-induced muscle wasting by improving myogenic gene expression, reducing atrophy markers, an...