| RRC ID |
86889
|
| 著者 |
Ikeda M, Tanaka Y, Sugihara H, Matsuwaki T, Yamanouchi K.
|
| タイトル |
Senescent-Like Myofibers Contribute to Anti-Regenerative Cytokine Signaling in Duchenne Muscular Dystrophy.
|
| ジャーナル |
FASEB J
|
| 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.
|
| 巻・号 |
40(4)
|
| ページ |
e71567
|
| 公開日 |
2026-2-28
|
| DOI |
10.1096/fj.202500098R
|
| PMID |
41725369
|
| PMC |
PMC12926723
|
| MeSH |
Animals
Cellular Senescence* / physiology
Cyclin-Dependent Kinase Inhibitor p16 / genetics
Cyclin-Dependent Kinase Inhibitor p16 / metabolism
Cytokines* / genetics
Cytokines* / metabolism
Male
Muscle Fibers, Skeletal* / metabolism
Muscle Fibers, Skeletal* / pathology
Muscle, Skeletal / metabolism
Muscular Dystrophy, Duchenne* / genetics
Muscular Dystrophy, Duchenne* / metabolism
Muscular Dystrophy, Duchenne* / pathology
Rats
Rats, Sprague-Dawley
Regeneration* / physiology
Signal Transduction*
|
| IF |
4.966
|
| リソース情報 |
| ラット |
LEW-Tg(CAG-EGFP)1Ys (StrainID=647) |
