Linc00657 promoted pyroptosis in THP-1-derived macrophages and exacerbated atherosclerosis via the miR-106b-5p/TXNIP/NLRP3 axis

This study was designed to investigate the effects and underlying mechanisms of linc00657 in atherogenesis. The results showed that ox-LDL treatment significantly induced pyroptosis in human THP-1-derived macrophages. The secretion levels of LDH and pro-inflammatory factors were markedly enhanced, and the integrity of plasma membranes was disrupted in ox-LDL-treated THP-1-derived macrophages. These effects were significantly compensated after transfection with linc00657 siRNA and became more evident by linc00657 overexpression. Moreover, the effects of linc00657 overexpression on pyroptosis of THP-1-derived macrophages can also be robustly reversed by TXNIP knockdown or miR-106b-5p mimics transfection. Mechanistically, linc00657 enhanced TXNIP expression by competitively binding to miR-106b-5p, promoting NLRP3 inflammasome activation. Finally, we found that linc00657 overexpression significantly increased the expression of pyroptosis-related factors and decreased miR-106b-5p level in the aorta of high-fat-diet-fed apoE-/- mice. Furthermore, linc00657 up-regulation enlarged the plaque area, exacerbated plasma lipid profile, and increased pro-inflammatory cytokines levels in the serum, effects that were reversed by injection of miR-106b-5p agomir. This evidence indicated that linc00657 stimulated macrophage pyroptosis and aggravated the progression of AS via the miR-106b-5p/TXNIP/NLRP3 pathway.PMID:37734516 | DOI:10.1016/j.ijbiomac.2023.126953
Source: International Journal of Biological Macromolecules - Category: Biochemistry Authors: Source Type: research