DNMT1/MTTP axis promotes gastritis progression during Helicobacter pylori infection by regulating GPX4 and
Chunli Tang1,2, Fanlai Meng3, Renjie Li4
1Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Background:
Helicobacter pylori (H. pylori)-induced chronic atrophic gastritis (CAG) is a significant health concern. The role of microsomal triglyceride transfer protein (MTTP) in CAG progression has not been explored, presenting a critical knowledge gap in understanding H. pylori-induced CAG pathogenesis.
Methods:
Sprague-Dawley rats and gastric epithelial cell line were infected with H. pylori to build CAG model. The mRNA and protein levels of DNA methyltransferase 1 (DNMT1), MTTP, and glutathione peroxidase 4 (GPX4) were measured by quantitative real-time PCR (RT-qPCR) and western blotting, respectively. Moreover, the localization of DNMT1 and MTTP was detected via immunohistochemistry. Furthermore, the pathological changes of gastric tissue were analyzed by HE staining.
Results:
The MTTP expression was downregulated in CAG. Moreover, overexpression of MTTP in gastric epithelial cells could suppress the inflammatory response induced by H. pylori infection and ferroptosis by upregulating GPX4 expression. In addition, DNMT1 expression was upregulated in CAG and was negatively correlated with MTTP expression. Furthermore, DNMT1 could target MTTP promoter to activate methylation and downregulate MTTP expression.
Conclusion:
DNMT1 downregulated the MTTP expression through methylation, and thus mediate inflammasome-ferroptosis processes via GPX4 in the H. pylori-induced CAG.
Insights
DNA methyltransferase 1 (DNMT1) downregulates microsomal triglyceride transfer protein (MTTP) via methylation, impacting inflammasome-ferroptosis pathways in Helicobacter pylori-induced chronic atrophic gastritis.
Area of Science:
- Gastroenterology
- Molecular Biology
- Pathogenesis Research
Background:
- Chronic atrophic gastritis (CAG) induced by Helicobacter pylori (H. pylori) presents a significant health challenge.
- The role of microsomal triglyceride transfer protein (MTTP) in H. pylori-induced CAG pathogenesis remains largely unexplored, highlighting a critical knowledge gap.
Purpose of the Study:
- To investigate the role of MTTP in the pathogenesis of H. pylori-induced chronic atrophic gastritis.
- To elucidate the relationship between MTTP, DNA methyltransferase 1 (DNMT1), and ferroptosis in CAG.
Main Methods:
- Established a CAG model in Sprague-Dawley rats and gastric epithelial cells infected with H. pylori.
- Quantified mRNA and protein levels of DNMT1, MTTP, and glutathione peroxidase 4 (GPX4) using RT-qPCR and western blotting.
- Analyzed pathological changes, and detected protein localization via HE staining and immunohistochemistry.
Main Results:
- MTTP expression was found to be downregulated in CAG.
- Overexpression of MTTP suppressed H. pylori-induced inflammation and ferroptosis by upregulating GPX4.
- DNMT1 expression was upregulated in CAG and negatively correlated with MTTP, with DNMT1 shown to methylate and downregulate MTTP.
Conclusions:
- DNMT1 downregulates MTTP expression through methylation.
- This DNMT1-mediated downregulation of MTTP influences inflammasome-ferroptosis pathways via GPX4 in H. pylori-induced CAG.
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