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| Status |
Public on Jun 01, 2022 |
| Title |
METTL3 Regulates LPS-Induced Inflammatory Response via the NOD1 Signaling Pathway |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Inflammation is normally a protective response to defend and restore homeostasis; nonresolving inflammation is a major driver of immune disorders. N6-methyladenosine (m6A) is a prevalent mRNA modification that plays a crucial function in multiple biological processes. The effect of m6A on the immune response has recently been reported. However, the effect is unclear, and the results are contradictory. In this study, the expression of total m6A and the methyltransferase METTL3 decreased in LPS-stimulated macrophages. METTL3 knockdown significantly upregulated expression of proinflammatory cytokines, including TNF-α, IL-6 and NO. RNA sequencing analysis showed that the upregulated genes were enriched in inflammation-related signaling pathways and that the NOD-like receptor signaling pathway might be the target molecules of METTL3. METTL3 depletion resulted in upregulation of the NOD1 pathway without impacting NOD2. Moreover, the increase in proinflammatory cytokines induced by METTL3 knockdown was reversed by blocking the NOD1 pathway using the NOD-IN-1 and ML130 specific inhibitors. Mechanistically, METTL3 knockdown promoted the mRNA expression and stability of NOD1 and RIPK2, and the same results were detected in m6A-binding protein YTHDF1- or YTHDF2-silenced cells. All findings suggested that METTL3 depletion inhibits the degradation of NOD1 and RIPK2 mRNA mediated by YTHDF1 and YTHDF2, which upregulate the NOD1 pathway and subsequently promote the LPS-induced inflammatory response in macrophages.
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| Overall design |
two repeates of mRNA from shControl RAW264.7 cells and two repeates of mRNA from shMETTL3 RAW264.7 cells
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| Contributor(s) |
Cai Y |
| Citation missing |
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| Submission date |
Nov 23, 2021 |
| Last update date |
Jun 01, 2022 |
| Contact name |
Yongjie Cai |
| E-mail(s) |
caiyj23@mail2.sysu.edu.cn
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| Phone |
18826073519
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| Organization name |
SUN YAT-SEN UNIVERSITY
|
| Lab |
Guangdong Provincial Key Laboratory of Stomatology
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| Street address |
56 Ling Yuan Xi Road
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| City |
Guangzhou |
| State/province |
Guangdong |
| ZIP/Postal code |
510055 |
| Country |
China |
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| Platforms (1) |
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| Samples (4)
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| Relations |
| BioProject |
PRJNA782970 |
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