Unraveling the Role of METTL3 in Helicobacter pylori-induced gastritis via m6A-CXCL1/NF-κB modulation
Qiutong Lu1, Zhaopeng Wang2, Shuixian Cao1
1Department of Gastroenterology, Jiangxi Provincial Key Laboratory of Digestive Diseases, Jiangxi Clinical Research Center for Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, PR China.
Abstract:
Helicobacter pylori (H. pylori) infection is a significant cause of gastric diseases, with its pathogenic mechanisms still not fully understood. This study investigates the role of METTL3, an enzyme involved in m6A methylation, in modulating the CXCL1/NF-κB signaling pathway in H. pylori-induced gastritis. Using both bioinformatics analysis of GEO database and experimental approaches including MeRIP, RIP assays, and immunostaining, this research highlights how METTL3 influences CXCL1 expression and NF-κB pathway activation. Results from both in vitro and in vivo models show that METTL3 increases inflammatory responses and apoptosis in gastric cells. Suppression of METTL3 resulted in decreased inflammation and apoptosis, suggesting its potential as a therapeutic target in gastritis management.
Insights
This study reveals METTL3 exacerbates inflammation and apoptosis in H. pylori gastritis by activating the CXCL1/NF-κB pathway. Inhibiting METTL3 reduces these harmful effects, identifying it as a potential therapeutic target for H. pylori infection.
Area of Science:
- Molecular biology
- Gastroenterology
- Immunology
Background:
- Helicobacter pylori infection is a primary cause of gastritis, but its pathogenic mechanisms require further elucidation.
- The role of RNA methylation, specifically N6-methyladenosine (m6A), in H. pylori-induced gastric disease is not well understood.
- METTL3, a key m6A methyltransferase, is implicated in various cellular processes, but its specific function in H. pylori gastritis needs investigation.
Purpose of the Study:
- To investigate the role of METTL3 in H. pylori-induced gastritis.
- To determine how METTL3 influences the CXCL1/NF-κB signaling pathway in gastric cells.
- To evaluate the therapeutic potential of targeting METTL3 in H. pylori gastritis.
Main Methods:
- Bioinformatic analysis of GEO database.
- Methylated RNA immunoprecipitation (MeRIP) and RNA immunoprecipitation (RIP) assays.
- Immunostaining in both in vitro and in vivo models of H. pylori gastritis.
Main Results:
- METTL3 was found to increase CXCL1 expression and activate the NF-κB signaling pathway.
- METTL3 significantly enhanced inflammatory responses and apoptosis in gastric cells during H. pylori infection.
- Suppression of METTL3 led to a notable reduction in inflammation and apoptosis.
Conclusions:
- METTL3 plays a crucial role in promoting inflammation and apoptosis in H. pylori-induced gastritis.
- Targeting METTL3 could be a promising therapeutic strategy for managing H. pylori-related gastric diseases.
- Understanding METTL3's role provides insights into the molecular pathogenesis of H. pylori infection.
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