DNMT1/MTTP axis promotes gastritis progression during Helicobacter pylori infection by regulating GPX4 and ferroptosis.

IF 3 4区医学 Q2 GENETICS & HEREDITY

Epigenomics Pub Date : 2025-06-09 DOI:10.1080/17501911.2025.2510187

Chunli Tang, Fanlai Meng, Renjie Li, Meimei Ma, Meiling Zhu, Chunfang Xu

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引用次数: 0

Abstract

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.

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DNMT1/MTTP轴通过调节GPX4和铁下垂促进幽门螺杆菌感染期间胃炎的进展。

背景：幽门螺杆菌（h.p ylori）诱导的慢性萎缩性胃炎（CAG）是一个重要的健康问题。微粒体甘油三酯转移蛋白（MTTP）在CAG进展中的作用尚未被探索，这在理解幽门螺杆菌诱导的CAG发病机制方面存在关键的知识空白。方法：采用spague - dawley大鼠和胃上皮细胞系感染幽门螺旋杆菌建立CAG模型。采用实时荧光定量PCR （RT-qPCR）和western blotting分别检测DNA甲基转移酶1 （DNMT1）、MTTP和谷胱甘肽过氧化物酶4 (GPX4) mRNA和蛋白水平。免疫组化检测DNMT1和MTTP的定位。并用HE染色分析大鼠胃组织的病理变化。结果：CAG中MTTP表达下调。此外，胃上皮细胞中过表达MTTP可通过上调GPX4的表达来抑制幽门螺杆菌感染和铁下垂引起的炎症反应。此外，DNMT1在CAG中表达上调，与MTTP表达呈负相关。此外，DNMT1可以靶向MTTP启动子激活甲基化，下调MTTP表达。结论：DNMT1通过甲基化下调MTTP表达，从而在幽门螺杆菌诱导的CAG中通过GPX4介导炎症小体-铁下沉过程。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Epigenomics GENETICS & HEREDITY-

CiteScore

5.80

自引率

2.60%

发文量

审稿时长

>12 weeks

期刊介绍： Epigenomics provides the forum to address the rapidly progressing research developments in this ever-expanding field; to report on the major challenges ahead and critical advances that are propelling the science forward. The journal delivers this information in concise, at-a-glance article formats – invaluable to a time constrained community. Substantial developments in our current knowledge and understanding of genomics and epigenetics are constantly being made, yet this field is still in its infancy. Epigenomics provides a critical overview of the latest and most significant advances as they unfold and explores their potential application in the clinical setting.