Skeletal muscle dysfunction in severe burns: identification of essential genes and drug discovery.

Abstract

Skeletal muscle dysfunction (SMD) is a common clinical feature among patients with severe burns and plays a crucial role in the recovery and prognosis of burn patients. However, the molecular targets and signal pathways of SMD after burns have not been fully understood, and there is an even greater lack of effective treatment measures. In this study, firstly, genes commonly related to SMD and functional recovery were obtained from the literature. Techniques included constructing protein-protein networks via the MCODE and cytoHubba plugins of Cytoscape, conducting GO analysis and KEGG analysis, and verifying the findings in animal models of severe burn-induced SMD by qRT-PCR. Subsequently, the key genes and signal pathways were determined by using GeneMANIA analysis. The transcription factors and ceRNA networks of the hub genes were identified, and the drug molecules that control the hub genes were obtained. Finally, molecular docking between gene targets and drug molecules was carried out, and the ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties of the drug molecules were verified. We identified 15 hub genes, and qRT-PCR results showed that 14 genes had significant differences, including IL6, TNF, IGF1, STAT3, IL10, AGT, LEP, CCL2, SIRT1, CASP3, MAPK3, PPARG, ALB, and IRS1. By analyzing the internal relationships, it was found that the gene STAT3 and the JAK/STAT3 pathway are the molecular targets and signal pathways of SMD. The transcription factors, ceRNA networks, and drug molecules were also determined. In addition, after molecular docking and ADMET analysis, it was found that the drug fluticasone performed excellently in all aspects. In conclusion, STAT3 was identified as the key target and signal pathway for functional recovery after SMD in burn patients.