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Sepsis–induced skeletal muscle wasting is ameliorated by the pharmacological inhibition of STAT3 signaling in mice [16S-Metagenome]

ABSTRACT: Septic patients frequently develop skeletal muscle wasting and weakness, which adversely affects survival and functional outcomes. Currently, no drugs are available for the treatment of sepsis-associated skeletal muscle wasting. Here, we tested the effects of C188-9, a STAT3-specific signaling inhibitor, on muscle wasting in vivo and myotube atrophy in vitro induced by sepsis. In mice, sepsis severity-dependently phosphorylated STAT3, which subsequently activated the ubiquitin–proteasome and autophagy proteolytic pathways, resulting in skeletal muscle atrophy. Similar dose-dependent responses were observed in lipopolysaccharide-treated C2C12 myotubes. In human septic patients, plasma interleukin-6 levels positively correlated with the extent of sepsis-associated skeletal muscle wasting. STAT3 inhibition in mice or cells treated with C188-9 suppressed activation of the ubiquitin–proteasome degradation pathway—but not autophagy pathways—and alleviated sepsis-associated skeletal muscle wasting. Overall, our results indicate that pharmacological inhibition of STAT3 signaling may represent a novel therapeutic strategy for sepsis-associated skeletal muscle wasting.

ORGANISM(S): mouse metagenome

PROVIDER: GSE299753 | GEO | 2026/02/11

REPOSITORIES: GEO

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Sepsis–induced skeletal muscle wasting is ameliorated by the pharmacological inhibition of STAT3 signaling in mice [RNA-seq]

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