Intestinal Epithelial Cell-specific Knockout of METTL3 Aggravates Intestinal Inflammation in CLP Mice by Weakening the Intestinal Barrier

作者：Hongzhou Shi, Jiahui Sun, Yaya Sun, Junjie Wu, Guangqing Jiang, Zhaiyue Xu, Xin Shi, Miao Fang · 发表于：Current Pharmaceutical Biotechnology · 年份：2024 · DOI：10.2174/0113892010271970240202054245 · 被引用次数：4 · 研究领域：Gut microbiota and health、Cancer-related gene regulation、Microbial metabolism and enzyme function

BACKGROUND: Many studies have demonstrated that the expression of methyltransferase- like 3 (METTL3) is altered in various inflammatory diseases. Its specific mechanistic role in the intestinal inflammatory response during sepsis remains limited and requires further investigation. OBJECTIVES: Explore the potential mechanism of METTL3 in the intestinal inflammatory response during sepsis. MATERIALS AND METHODS: Immunohistochemical analysis was utilized to detect the expression of METTL3 in the necrotic intestine of patients with intestinal necrosis and the small intestine of cecal ligation and puncture (CLP) mice. Mice were subjected to the CLP and Sham surgeries, intestine tissue was harvested and performed HE staining, and ELISA to examine intestinal inflammatory responses, while TUNEL staining was applied to detect intestinal cell apoptosis. Additionally, ELISA was used to detect diamine oxidase (DAO) and intestinal fatty acid binding protein (I-FABP) levels in intestinal tissue. Immunohistochemistry and RT-qPCR were also employed to examine the mRNA and protein expression levels of Zona Occludens 1 (ZO-1) and Claudin-1. Finally, transcriptomic sequencing was performed on the small intestine tissues of METTL3 Knock-out (KO) and Wild-type (WT) mice in response to sepsis. RESULTS: METTL3 exhibited lower expression level in the necrotic intestine of patients and the small intestine of CLP mice. Loss of METTL3 in CLP mice triggered significantly higher expression of TNF-α and I...