The interaction of HT-2 toxin and Akt1 on gene expression regulation in Kashin-Beck disease pathogenesis.

This study investigates the effects of T-2 toxin metabolite HT-2 alone or combined with Akt1 on chondrocyte gene expression to elucidate their roles in Kashin-Beck disease (KBD) pathogenesis. Lentiviral transfection was employed to silence Akt1 in C28/I2 human chondrocytes. High-throughput RNA sequencing and bioinformatics analysis methods were used to identify and compare differentially expressed genes (DEGs) and pathways in HT-2, siAkt1, HT-2-siAkt1 and Control (non-treatment) group. Co-expressed genes and co-expressed modules were investigated using WGCNA. Protein-protein interaction (PPI) networks were constructed using the STRING database, and hub genes were identified by the MCC algorithm. A total of 2086 DEGs were identified in the HT-2 vs Control comparison, with significant upregulation observed for CCND2, MMP9 and TIMP4. The adhesion and PI3K-Akt signaling pathways were upregulated, while ECM-receptor interactions was downregulated. In the siAkt1 vs Control comparison, 695 DEGs were detected. VAMP7 and CXCR4 were significantly upregulated, while PFKL and ALDOA were significantly downregulated. Fructose and mannose metabolism, amino acid biosynthesis, and glucose/energy metabolic pathways were significantly downregulated. There were 411 DEGs when HT-2-siAkt1 vs HT-2, and CCND2, MMP9, WTAPP1 and TIMP4 were significantly downregulated. Adhesion, NF-κB signaling pathway and PI3K-Akt signaling pathway were significantly downregulated. Under, WGCNA, in the module most associated with HT-2, FRMD3B, ALDH1A3, ANTXR2, SERINC2 and SRGN were identified as hub genes; in the module most associated with siAkt1, TNFRSF11B, CECR2, TMOD1, ZNF704 and RHOBTB1 were identified as hub genes; in the module most associated with HT-2-siAkt1, the hub genes were GNAL, SLC25A32, ACADSB, CABLES1 and GINS4. Akt1 primarily affects the expression of genes in chondrocytes under HT-2 exposure that involved in autophagy, cell proliferation and glycolysis and other cell functions, potentially contributing to the pathogenesis of KBD.