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Mettl3 promotes oxLDL-mediated inflammation through activating STAT1 signaling

Zhenwei Li1,2, Qingqing Xu3, Ning Huangfu2

  • 1Department of Cardiology, The first Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Journal of Clinical Laboratory Analysis
|November 26, 2021
PubMed
Abstract

Insights

Methyltransferase-Like Protein 3 (Mettl3) promotes inflammation in atherosclerosis by modifying Signal transducer and activator of transcription 1 (STAT1) mRNA in macrophages. This suggests Mettl3 as a potential therapeutic target for atherosclerosis.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cardiovascular Research

Background:

  • Atherosclerosis (AS) is a primary cause of cerebrovascular diseases.
  • Macrophages play a critical role in AS pathogenesis by regulating inflammation.
  • The role of N(6)-methyladenine (m6A) RNA modification in AS remains largely unknown.

Purpose of the Study:

  • To investigate the role of m6A modification in inflammation triggered by oxidized low-density lipoprotein (oxLDL) in macrophages.
  • To elucidate the underlying mechanisms of m6A modification in oxLDL-induced inflammation.

Main Methods:

  • RAW264.7 macrophage cells were stimulated with ox-LDL.
  • Techniques included Dot blot, Immunoprecipitation, Western blot, and RIP-ChIP experiments.

Main Results:

  • OxLDL stimulation increased mRNA m6A modification in macrophages.
  • Knockdown of Methyltransferase-Like Protein 3 (Mettl3) inhibited oxLDL-induced m6A modification and inflammation.
  • Mettl3 regulates oxLDL-induced inflammation via m6A modification of Signal transducer and activator of transcription 1 (STAT1) mRNA, impacting STAT1 expression and activation.
  • OxLDL enhanced Mettl3-STAT1 interaction, promoting STAT1-mediated inflammatory gene expression.

Conclusions:

  • Mettl3 promotes oxLDL-triggered inflammation in macrophages by interacting with STAT1 protein and mRNA.
  • Mettl3 represents a potential therapeutic target for clinical treatment of atherosclerosis.
Keywords:
N6-methyladenosineatherosclerosisinflammationmethyltransferase-like protein 3signal transducer and activator of transcription 1

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