Peli1, regulated by m6A modification, suppresses NLRP3 inflammasome activation in atherosclerosis by inhibiting YB-1

• DOI: 10.1038/s42003-025-07839-w
• Publication Date: 2025-03-19T01:48:56Z
• Authors: Qiang Liu; Lu Yan; Tao Wu; Qinghua Wu; Ben Ke; Wen Shen
• Keywords: Surface Modification

The activation of pyrin domain-containing-3 (NLRP3) inflammasome in macrophages is a risk factor accelerating the progression atherosclerosis (AS). Here, function pellino 1 (Peli1) regulating NLRP3 during development AS was investigated. Our results showed that Y-box binding protein (YB-1) knockdown could inhibit vivo, and YB-1 silencing repressed oxidized low-density lipoprotein (ox-LDL)-mediated lipid accumulation inflammation by inactivating inflammasome. E3 ubiquitination ligase Peli1 mediated ubiquitination-dependent degradation progression. Moreover, it found YTH domain-containing 2 (YTHDC2) recognized methyltransferase-like 3 (METTL3)-mediated N6-methyladenosine (m6A) modification mRNA degradation. Rescue studies revealed upregulation abrogated repressive effect on both vitro vivo. Taken together, Peli1, regulated m6A modification, inhibited YB-1-mediated promoting to suppress AS. inhibits atherosclerosis.