Published online Apr 15, 2024. doi: 10.4239/wjd.v15.i4.735
Peer-review started: November 11, 2023
First decision: January 15, 2024
Revised: January 21, 2024
Accepted: March 4, 2024
Article in press: March 4, 2024
Published online: April 15, 2024
Processing time: 152 Days and 8.4 Hours
The cognitive impairment in type 2 diabetes mellitus (T2DM) is a multifaceted and advancing state that requires further exploration to fully comprehend. Neu
To identify and validate the immune-related genes in the hippocampus associated with T2DM-related cognitive impairment.
To identify differentially expressed genes (DEGs) between T2DM and controls, we used data from the Gene Expression Omnibus database GSE125387. To identify T2DM module genes, we used Weighted Gene Co-Expression Network Analysis. All the genes were subject to Gene Set Enrichment Analysis. Protein-protein interaction network construction and machine learning were utilized to identify three hub genes. Immune cell infiltration analysis was performed. The three hub genes were validated in GSE152539 via receiver operating characteristic curve analysis. Validation experiments including reverse transcription quantitative real-time PCR, Western blotting and immunohistochemistry were conducted both in vivo and in vitro. To identify potential drugs associated with hub genes, we used the Comparative Toxicogenomics Database (CTD).
A total of 576 DEGs were identified using GSE125387. By taking the intersection of DEGs, T2DM module genes, and immune-related genes, a total of 59 genes associated with the immune system were identified. Afterward, machine learning was utilized to identify three hub genes (H2-T24, Rac3, and Tfrc). The hub genes were associated with a variety of immune cells. The three hub genes were validated in GSE152539. Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro, consistent with the bioinformatics analysis. Additionally, 11 potential drugs associated with RAC3 and TFRC were identified based on the CTD.
Immune-related genes that differ in expression in the hippocampus are closely linked to microglia. We validated the expression of three hub genes both in vivo and in vitro, consistent with our bioinformatics results. We discovered 11 compounds associated with RAC3 and TFRC. These findings suggest that they are co-regulatory molecules of immunometabolism in diabetic cognitive impairment.
Core Tip: Using GSE125387, we identified differentially expressed genes in the hippocampus of T2DM mice and controls. Fifty-nine genes were identified through functional enrichment analysis and protein-protein interactions analysis. Machine learning was utilized to identify three hub genes (H2-T24, Rac3, and Tfrc). And the three hub genes were validated in GSE152539. Validation experiments were conducted at the mRNA and protein levels both in vivo and in vitro. Additionally, 11 potential compands associated with RAC3 and TFRC were identified based on the Comparative Toxicogenomics Data