Identifying Autophagy-Related Genes contributing to Diabetes Peripheral Neuropathy

Abstract Purpose Diabetes has a common complication called diabetic peripheral neuropathy (DPN), whose exact pathophysiology is still unknown. In ischemic reperfusion injury to nerve tissues, the treatment of neurodegenerative illnesses, and the repair of nerve tissue injuries, autophagy is crucial. Through bioinformatics analysis and validation, we hope to pinpoint the possible autophagy-related differential expressed genes (DEGs) of DPN. Methods The GEO database provided the mRNA expression profile dataset GSE185011. R software was used to look for possible DPN autophagy-related DEGs. Then, for the autophagy-related DEGs, protein-protein interactions (PPI), correlation analysis, gene-ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out. In the validation set GSE95849, the RNA expression of autophagy-related DEGs was verified in blood samples from DPN patients and healthy controls. Results Between 5 DPN patients and 5 healthy controls, a total of 33 autophagy-related DEGs (5 up-regulated genes and 28 down-regulated genes) were found. The PPI analysis showed interactions between these autophagy-related DEGs. The GO and KEGG enrichment analyses revealed a number of enriched terms including mitophagy and autophagy. The results of the validation set demonstrated that the expression levels of the genes P4HB, GAPDH, CTSB and RAB7A were significantly decreased, ATG5, CASP3, SQSTM1, ULK1, and 9 other genes in DPN patients were significantly up-regulated in the DPN patients, which were compatible with the bioinformatics analysis of mRNA microarray. Conclusion Through bioinformatics research, we identified 17 putative autophagy-related DEGs in DPN. By regulating autophagy, ATG5, CASP3, SQSTM1, ULK1, and another 13 genes may have an impact on DPN formation. These findings might deepen our understanding of DPN and help with DPN treatment.