CircANKRD36 Knockdown Inhibits M1 Polarization and Inflammatory Response via miR‐498/TXNRD1 in LPS‐Stimulated Macrophages Under High Glucose Conditions

Macrophage polarization and inflammation play a pivotal role in bone healing disorders in diabetes. This study aimed to investigated the effect and mechanism of circANKRD36 on M1 polarization and inflammatory response in LPS-stimulated macrophages under high glucose conditions. Our results showed that high glucose promoted circANKRD36 expression, the proportion of CD11b⁺CD86⁺ cells, and mRNA and protein levels of M1-type pro-inflammatory factors IL-1β, TNF-α, and iNOS in LPS-stimulated macrophages, while reducing miR-498 expression. The interaction between circANKRD36 and miR-498 was predicted by ENCORI and proved by the luciferin experiment. circANKRD36 knockdown downregulated the proportion of CD11b⁺CD86⁺ cells and the expression of IL-1β, TNF-α, and iNOS in LPS-stimulated macrophages under high glucose conditions, whereas miR-498 knockdown reversed these effects. Moreover, high-throughput mRNA sequencing and bioinformatic analysis revealed that, compared to LPS-stimulated macrophages under high glucose conditions, the differentially expressed genes (DEG) in those with circANKRD36 knockdown were enriched in AGE-RAGE signaling pathway, while the DEG in those with miR-498 knockdown were enriched in NF-κB, MAPK, and TNF signaling pathways. Based on sequencing data and bioinformatics prediction, we identified TXNRD1 as the downstream target gene. TXNRD1 expression decreased with circANKRD36 knockdown but increased with miR-498 knockdown in LPS-stimulated macrophages under high glucose conditions. TXNRD1 overexpression reversed the effects of circANKRD36 knockdown in LPS-stimulated macrophages under high glucose conditions. In conclusion, circANKRD36 knockdown could inhibit M1 polarization and inflammatory response via miR-498/TXNRD1 in macrophages under high glucose and inflammatory conditions.