التفاصيل البيبلوغرافية
| العنوان: |
METTL14 contributes to acute lung injury by stabilizing NLRP3 expression in an IGF2BP2-dependent manner |
| المؤلفون: |
Fei Cao, Guojun Chen, Yixin Xu, Xintong Wang, Xiaole Tang, Wenyu Zhang, Xiong Song, Xiaohua Yang, Weian Zeng, Jingdun Xie |
| المصدر: |
Cell Death and Disease, Vol 15, Iss 1, Pp 1-15 (2024) |
| بيانات النشر: |
Nature Publishing Group, 2024. |
| سنة النشر: |
2024 |
| المجموعة: |
LCC:Cytology |
| مصطلحات موضوعية: |
Cytology, QH573-671 |
| الوصف: |
Abstract Acute lung injury (ALI) as well as its more severe form, acute respiratory distress syndrome (ARDS), frequently leads to an uncontrolled inflammatory response. N6-methyladenosine (m6A) modification was associated with the progression of several inflammatory diseases. However, the role of methyltransferase-like 14 (METTL14)-mediated m6A methylation in ALI/ARDS remains unclear. Here, we reported an increase in overall expression levels of m6A and METTL14 in circulating monocyte-derived macrophages recruited to the lung following ALI, which is correlated with the severity of lung injury. We further demonstrated the critical function of METTL14 in activating NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in vitro and in mouse models of ALI/ARDS, and validated NLRP3 as the downstream target of METTL14 by the m6A RNA immunoprecipitation (MeRIP) and RIP assays. Mechanistically, METTL14-methylated NLRP3 transcripts were subsequently recognized by insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an m6A reader, which stabilized NLRP3 mRNA. Furthermore, we observed that IGF2BP2 knockdown diminished LPS-induced ALI in mice by downregulating NLRP3 expression. In summation, our study revealed that the molecular mechanism underlying the pathogenesis of ALI/ARDS involves METTL14-mediated activation of NLRP3 inflammasome in an IGF2BP2 dependent manner, thereby demonstrating the potential of METTL14 and IGF2BP2 as promising biomarkers and therapeutic targets for ALI/ARDS treatment. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
2041-4889 |
| Relation: |
https://doaj.org/toc/2041-4889 |
| DOI: |
10.1038/s41419-023-06407-6 |
| URL الوصول: |
https://doaj.org/article/e222e3bfd77b4f8da35499f1e30ad0ed |
| رقم الانضمام: |
edsdoj.222e3bfd77b4f8da35499f1e30ad0ed |
| قاعدة البيانات: |
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