Ankrd2 may alleviate denervation-induced skeletal muscle atrophy by inhibiting inflammation.

Background/aim: Sciatic nerve injury causes a loss of skeletal muscle innervation, reduced motor function, and eventual muscle atrophy. Inflammation and increased protein degradation are key factors contributing to muscle atrophy. Inflammation is activated early during muscle atrophy and can be modulated by various factors. However, the precise role of inflammation in denervation-induced muscle atrophy remains unclear. Materials and methods: Transcriptome sequencing was used to determine that the inflammatory response occurs early during denervation-induced muscle atrophy. RT-qPCR validation of several inflammatory factors showed rapid upregulation at early stages, followed by gradual downregulation. Weighted gene coexpression network analysis of differentially expressed genes identified gene modules whose expression patterns were correlated with or inversely correlated to the inflammatory phenotype, thereby identifying key regulatory factors. A total of 14 coexpression modules were identified, and expression patterns opposite to those of inflammatory factors were examined to investigate potential regulatory molecules that could inhibit inflammation and protect skeletal muscle. Results: Ankrd2 was identified in the darkorange module, showing no significant change at 36 h postdenervation, followed by gradual upregulation, which was opposite to the expression of inflammatory factors. An Ankrd2-overexpressing lentivirus was injected into the tibialis anterior muscle, and Ankrd2 overexpression was found to significantly alleviate muscle atrophy. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that Ankrd2 overexpression was associated with downregulation of inflammation-related pathways, particularly the NF-κB signaling pathway. Proatrophy genes in both the ubiquitin-proteasome and autophagic-lysosomal systems were also suppressed. Conclusion: The present study suggests that denervation-induced muscle atrophy is alleviated by Ankrd2, potentially through inhibition of inflammation, highlighting its potential as a therapeutic target.