Protective Effect of Delta-Like 1 Homolog Against Muscular Atrophy in a Mouse Model

다국어 초록 (Multilingual Abstract)

Background: Muscle atrophy is caused by an imbalance between muscle growth and wasting. Delta-like 1 homolog (DLK1), a protein that modulates adipogenesis and muscle development, is a crucial regulator of myogenic programming. Thus, we investigatedthe effect of exogenous DLK1 on muscular atrophy.
Methods: We used muscular atrophy mouse model induced by dexamethasone (Dex). The mice were randomly divided into threegroups: (1) control group, (2) Dex-induced muscle atrophy group, and (3) Dex-induced muscle atrophy group treated with DLK1.
The effects of DLK1 were also investigated in an in vitro model using C2C12 myotubes.
Results: Dex-induced muscular atrophy in mice was associated with increased expression of muscle atrophy markers and decreasedexpression of muscle differentiation markers, while DLK1 treatment attenuated these degenerative changes together with reducedexpression of the muscle growth inhibitor, myostatin. In addition, electron microscopy revealed that DLK1 treatment improved mitochondrial dynamics in the Dex-induced atrophy model. In the in vitro model of muscle atrophy, normalized expression of muscledifferentiation markers by DLK1 treatment was mitigated by myostatin knockdown, implying that DLK1 attenuates muscle atrophythrough the myostatin pathway.
Conclusion: DLK1 treatment inhibited muscular atrophy by suppressing myostatin-driven signaling and improving mitochondrialbiogenesis. Thus, DLK1 might be a promising candidate to treat sarcopenia, characterized by muscle atrophy and degeneration.

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