Transcriptome sequencing analysis reveals the molecular mechanism of sepsis-induced muscle atrophy.

Abstract

Background: Sepsis-induced skeletal muscle atrophy is accompanied by complex physiological and biochemical changes that negatively affect clinical outcomes, lead to prolonged hospitalization, and even increase mortality. However, few studies have been performed on the mechanisms of the disease, and effective treatments are still lacking. This study is aimed to research the molecular mechanisms of sepsis-induced skeletal muscle atrophy and to develop new therapeutic strategies.

Methods: In this study, we first constructed a mouse model of sepsis after cecal ligation and puncture (CLP). At 12, 24, 48, and 72 hours after modeling, we then analyzed the differentially expressed genes (DEGs) in the tibialis anterior muscle using transcriptome sequencing technology.

Results: The results showed that tibialis anterior muscle atrophy exacerbated with time after CLP and was accompanied by the altered expression of a large number of genes. The expression profiling analysis showed that there were three transcriptional phases within 72 hours of surgery: transcriptional phase I (0-12 hours), transcriptional phase II (24 hours), and transcriptional phase III (48-72 hours), of which 24 hours may be the critical time point for muscle atrophy. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the upregulated genes were mainly involved in inflammatory immunity, proteolysis, apoptosis, and autophagy, while the downregulated genes were mainly involved in cell proliferation and protein synthesis. These three transcriptional phases were defined as the inflammatory-immune phase, inflammatory-atrophy phase, and atrophy phase, respectively.

Conclusions: These findings not only enrich understandings of the molecular mechanism of sepsis-induced skeletal muscle atrophy, but also provide a scientific basis for its targeted therapy.