DNMT1/MTTP轴通过调节GPX4和铁死亡促进感染期间胃炎的进展。
DNMT1/MTTP axis promotes gastritis progression during infection by regulating GPX4 and ferroptosis.
作者信息
Tang Chunli, Meng Fanlai, Li Renjie, Ma Meimei, Zhu Meiling, Xu Chunfang
机构信息
Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou, China.
Department of Gastroenterology, The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian, China.
出版信息
Epigenomics. 2025 Jul;17(10):647-659. doi: 10.1080/17501911.2025.2510187. Epub 2025 Jun 9.
BACKGROUND
-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 -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 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 -induced CAG.
背景
幽门螺杆菌诱导的慢性萎缩性胃炎（CAG）是一个重大的健康问题。微粒体甘油三酯转运蛋白（MTTP）在CAG进展中的作用尚未得到探索，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
用幽门螺杆菌感染Sprague-Dawley大鼠和胃上皮细胞系以建立CAG模型。分别通过定量实时PCR（RT-qPCR）和蛋白质印迹法检测DNA甲基转移酶1（DNMT1）、MTTP和谷胱甘肽过氧化物酶4（GPX4）的mRNA和蛋白质水平。此外，通过免疫组织化学检测DNMT1和MTTP的定位。此外，通过苏木精-伊红（HE）染色分析胃组织的病理变化。
结果
CAG中MTTP表达下调。此外，胃上皮细胞中MTTP的过表达可通过上调GPX4表达来抑制幽门螺杆菌感染诱导的炎症反应和铁死亡。此外，CAG中DNMT1表达上调，且与MTTP表达呈负相关。此外，DNMT1可靶向MTTP启动子以激活甲基化并下调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中介导炎性小体-铁死亡过程。
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