Skeletal muscle atrophy is a prevalent complication of chronic kidney disease (CKD) and serves as an indicator of adverse prognosis and poor quality of life
however, the underlying mechanisms remain ambiguous. Emerging evidence has shown that long non-coding RNAs (lncRNAs) are involved in the pathogenesis of skeletal muscle atrophy. Using RNA sequencing (RNA-seq), we discerned elevated GAS5 expression in the muscles of CKD mice and verified these findings by real-time qPCR. Transmission electron microscopy confirmed morphological signs of pyroptosis, a potentially causal cellular death form. Additionally, elevated levels of pyroptosis markers, such as NLRP3, cleaved caspase-1, and GSDMD-N, were observed in CKD mouse models and lipopolysaccharide (LPS)/ATP-stimulated C2C12 myotubes. Intriguingly, the knockdown of GAS5 reduced these markers, alleviating pyroptosis and enhancing myofiber size, both