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.

Epigenomics
|June 9, 2025
PubMed
Abstract

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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