Authors
Young Hoon Son, Christina Y Sheng, Ji-Eun Jeong, Yuri Choi, Hyocheol Jung, Jihee Won, Audrey Atinsky, Junbeom Park, Jin Chul Kim, Keel Yong Lee, Young Il Park, Sung-Jin Park
Published in
Biochip journal. Volume 20. Issue 3. Pages 562-578. Epub Jun 11, 2026.
Abstract
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, and enhancing muscle contractility (baseline stress restored by ~ 77%, n = 6-9 per group, p < 0.05). Extending these findings to cardiac tissues, we demonstrated irisin's protective effects against DEX-induced cardiotoxicity using a human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) model (irisin significantly improved contractile amplitude and reduced cell death indices in DEX-treated hiPSC-CMs, p < 0.05). This study underscores the utility of engineered muscle platforms for investigating irisin's therapeutic mechanisms. The demonstrated protective effects of irisin highlight its potential as a translatable therapeutic agent for muscle wasting and cardiac dysfunction. These platforms provide valuable insights into the systemic benefits of exercise-induced myokines and pave the way for developing exercise-mimetic therapies targeting muscle and cardiac disorders.
The online version contains supplementary material available at 10.1007/s13206-026-00268-9.
PMID:
42564230
Bibliographic data and abstract were imported from PubMed on 07 Aug 2026.
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