2026-02-23 東京大学
DMDラットでは筋線維にp16発現を介したサイトカイン(SASP)発現上昇がおこることで筋再生に不利な体内環境が作られている
<関連情報>
- https://www.a.u-tokyo.ac.jp/topics/topics_20260223-1.html
- https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202500098R
老化様筋線維はデュシェンヌ型筋ジストロフィーにおける抗再生性サイトカインシグナル伝達に寄与する Senescent-Like Myofibers Contribute to Anti-Regenerative Cytokine Signaling in Duchenne Muscular Dystrophy
Masanari Ikeda, Yukie Tanaka, Hidetoshi Sugihara, Takashi Matsuwaki, Keitaro Yamanouchi
The FASEB Journal Published: 23 February 2026
DOI:https://doi.org/10.1096/fj.202500098R
ABSTRACT
Duchenne muscular dystrophy (DMD) is a genetic muscular disease characterized by progressive muscle degeneration. p16 is expressed in skeletal muscles and induces cellular senescence in a rat model of DMD, whereas its ablation enhances muscle regeneration. However, the mechanism underlying this phenomenon remains unclear. This study aimed to elucidate the mechanism for p16-induced DMD exacerbation. RNA-seq analysis revealed p16-dependent upregulation of cytokine gene expression in DMD rat skeletal muscles, which also altered the systemic blood cytokine profile. Furthermore, the effect of an altered humoral environment on muscle regeneration was assessed using the transplanted extensor digitorum longus muscle. Regeneration of grafted muscles from wild-type rats was suppressed in DMD rats but was significantly improved by p16 ablation. Notably, p16 was expressed in the myofibers of DMD rats, and enzymatically isolated myofibers from DMD rats also showed p16-dependent cytokine expression. Thus, cytokines secreted by senescent-like myofibers mediate the anti-regenerative niche in DMD rats, uncovering a novel mechanism for disease progression and potential therapeutic targets.
