Scholarlink

<p>The activation of pyrin domain-containing-3 (NLRP3) inflammasome in macrophages is a risk factor accelerating the progression of atherosclerosis (AS). Here, the function of pellino 1 (Peli1) in regulating the activation of NLRP3 inflammasome during the development of AS was investigated. Our results showed that Y-box binding protein 1 (YB-1) knockdown could inhibit the progression of AS in vivo, and YB-1 silencing repressed oxidized low-density lipoprotein (ox-LDL)-mediated lipid accumulation and inflammation in macrophages by inactivating NLRP3 inflammasome. E3 ubiquitination ligase Peli1 mediated ubiquitination-dependent degradation of YB-1 during AS progression. Moreover, it was found that YTH domain-containing 2 (YTHDC2) recognized methyltransferase-like 3 (METTL3)-mediated Peli1 N6-methyladenosine (m<sup>6</sup>A) modification and mediated Peli1 mRNA degradation. Rescue studies revealed that YB-1 upregulation abrogated the repressive effect of Peli1 upregulation on AS progression both in vitro and in vivo. Taken together, Peli1, regulated by m<sup>6</sup>A modification, inhibited YB-1-mediated activation of NLRP3 inflammasome in macrophages by promoting YB-1 ubiquitination to suppress the progression of AS.</p><p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

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

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年3月19日

查看全文
  • Qiang Liu,
  • Lu Yan,
  • Tao Wu,
  • Qinghua Wu,
  • Ben Ke,
  • Wen Shen

摘要

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