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Review
. 2023 Aug 21:14:1221609.
doi: 10.3389/fimmu.2023.1221609. eCollection 2023.

Emerging role of METTL3 in inflammatory diseases: mechanisms and therapeutic applications

Bimei Song  1 , Yue Zeng  1 , Yanqing Cao  1 , Jiamin Zhang  1 , Chao Xu  1 , Yaping Pan  1 , Xida Zhao  1 , Jingbo Liu  1
Affiliations
Review

Emerging role of METTL3 in inflammatory diseases: mechanisms and therapeutic applications

Bimei Song et al. Front Immunol. .

Abstract

Despite improvements in modern medical therapies, inflammatory diseases, such as atherosclerosis, diabetes, non-alcoholic fatty liver, chronic kidney diseases, and autoimmune diseases have high incidence rates, still threaten human health, and represent a huge financial burden. N6-methyladenosine (m6A) modification of RNA contributes to the pathogenesis of various diseases. As the most widely discussed m6A methyltransferase, the pathogenic role of METTL3 in inflammatory diseases has become a research hotspot, but there has been no comprehensive review of the topic. Here, we summarize the expression changes, modified target genes, and pathogenesis related to METTL3 in cardiovascular, metabolic, degenerative, immune, and infectious diseases, as well as tumors. In addition to epithelial cells, endothelial cells, and fibroblasts, METTL3 also regulates the function of inflammation-related immune cells, including macrophages, neutrophils, dendritic cells, Th17 cells, and NK cells. Regarding therapeutic applications, METTL3 serves as a target for the treatment of inflammatory diseases with natural plant drug components, such as emodin, cinnamaldehyde, total flavonoids of Abelmoschus manihot, and resveratrol. This review focuses on recent advances in the initiation, development, and therapeutic application of METTL3 in inflammatory diseases. Knowledge of the specific regulatory mechanisms involving METTL3 can help to deepen understanding of inflammatory diseases and lay the foundation for the development of precisely targeted drugs to address inflammatory processes.

Keywords: METTL3; immune cell; inflammation; inflammatory diseases; m6A modification; therapy.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The role of METTL3 in regulating macrophage inflammation and polarization.
Figure 2
Figure 2
The effects of METTL3 and m6A reader proteins mentioned in this review on RNA modification and metabolism. Figure Legends: METTL3 adds the m6A motif to RNA. HNRNPA2B1 recognizes m6A in the nucleus and promotes miRNA maturation. IGF2BP1/2 recognizes m6A in the nucleus and promotes mRNA stability. YTHDF1 recognizes m6A in the cytoplasm and enhances mRNA translation. YTHDF2 recognizes m6A in the cytoplasm and promotes mRNA decay.
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References

    1. Medzhitov R. Inflammation 2010: new adventures of an old flame. Cell (2010) 140:771–6. doi: 10.1016/j.cell.2010.03.006 - DOI - PubMed
    1. Medzhitov R. Origin and physiological roles of inflammation. Nature (2008) 454:428–35. doi: 10.1038/nature07201 - DOI - PubMed
    1. Kotas ME, Medzhitov R. Homeostasis, inflammation, and disease susceptibility. Cell (2015) 160:816–27. doi: 10.1016/j.cell.2015.02.010 - DOI - PMC - PubMed
    1. Weiss U. Inflammation. Nature (2008) 454:427–7. doi: 10.1038/454427a - DOI - PubMed
    1. Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell (2010) 140:805–20. doi: 10.1016/j.cell.2010.01.022 - DOI - PubMed

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