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The cGAS-STING pathway contributes to cisplatin-induced skeletal muscle atrophy through altered proteostasis and myogenic signaling - PubMed

6 hours ago
  • #Skeletal muscle
  • #Chemotherapy-induced atrophy
  • #cGAS-STING pathway
  • The cGAS-STING pathway is implicated in cisplatin-induced skeletal muscle atrophy.
  • Pharmacological activation of STING with DMXAA worsened cisplatin-induced muscle atrophy.
  • Genetic deletion of cGAS or STING attenuated cisplatin-induced muscle atrophy in mice.
  • Muscle-specific cGAS knockout preserved muscle weight and fiber diameter after cisplatin treatment.
  • RNA sequencing revealed altered inflammatory signaling, proteasome function, and autophagy pathways.
  • Reduced expression of atrophy genes (FBXO32, Murf1) and preserved myogenic regulators in cGAS-deficient mice.
  • NF-κB signaling and interferon-stimulated gene expression were diminished.
  • Targeting the cGAS-STING pathway may be a therapeutic strategy to prevent chemotherapy-induced muscle atrophy.