| Autor: |
Yuan Jiang, Huiyu Liu, Ruimin Shi, Yingying Hao, Junting Zhang, Wei Xin, Yiying Li, Cui Ma, Xiaodong Zheng, Lixin Zhang, Xijuan Zhao, Daling Zhu |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, Vol 13, Iss 19 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2047-9980 |
| DOI: |
10.1161/JAHA.124.034470 |
| Popis: |
Background Pulmonary hypertension is a rare, progressive disorder that can lead to right ventricular hypertrophy, right heart failure, and even sudden death. N6‐methyladenosine modification and the main methyltransferase that mediates it, methyltransferase‐like (METTL) 3, exert important effects on many biological and pathophysiological processes. However, the role of METTL3 in pyroptosis remains unclear. Methods and Results Here, we characterized the role of METTL3 and the underlying cellular and molecular mechanisms of pyroptosis, which is involved in pulmonary hypertension. METTL3 was downregulated in a pulmonary hypertension mouse model and in hypoxia‐exposed pulmonary artery smooth muscle cell. The small interfering RNA–induced silencing of METTL3 decreased the m6A methylation levels and promoted pulmonary artery smooth muscle cell pyroptosis, mimicking the effects of hypoxia. In contrast, overexpression of METTL3 suppressed hypoxia‐induced pulmonary artery smooth muscle cell pyroptosis. Mechanistically, we identified the phosphate and tension homology deleted on chromosome 10 (PTEN) gene as a target of METTL3‐mediated m6A modification, and methylated phosphate and tension homology deleted on chromosome 10 mRNA was subsequently recognized by the m6A “reader” protein insulin‐like growth factor 2 mRNA‐binding protein 2, which directly bound to the m6A site on phosphate and tension homology deleted on chromosome 10 mRNA and enhanced its stability. Conclusions These results identify a new signaling pathway, the METTL3/phosphate and tension homology deleted on chromosome 10/insulin‐like growth factor 2 mRNA‐binding protein 2 axis, that participates in the regulation of hypoxia‐induced pyroptosis. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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