DNMT1/miR-130a/ZEB1 Regulatory Pathway Affects the Inflammatory Response in Lipopolysaccharide-Induced Sepsis.

IF 2.6 4区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY DNA and cell biology Pub Date : 2022-04-29 DOI:10.1089/dna.2021.1060
Jurong Ding, Hong-bin Jiang, B. Su, Shanmei Wang, Xiaolan Chen, Yanlin Tan, L. Shen, Jingjing Wang, M. Shi, Haixu Lin, Zhemin Zhang
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引用次数: 2

Abstract

Sepsis is a global health care issue that affects millions of people. DNA methyltransferase I (DNMT1)-mediated DNA methylation is involved in a number of human diseases by affecting many types of cellular progression events. However, the role and underlying molecular mechanism of DNMT1 in development of sepsis remain largely unknown. Lipopolysaccharide (LPS) induced lung fibrosis in the sepsis mouse model, and DNMT1 was upregulated in lung tissues of a sepsis mouse model compared with lung tissues from control mice. Then, this study demonstrated that LPS induced the production of interleukin (IL)-7 and tumor necrosis factor (TNF)-α and promoted DNMT1 expression in primary type II alveolar epithelial cells (AECII cells). Knockdown of DNMT1 inhibited IL-7 and TNF-α secretion in AECII cells exposed to LPS. Further study demonstrated that DNMT1 repressed the expression of miR-130a in AECII cells with or without LPS exposure. Next, this study demonstrated that miR-130a inhibited ZEB1 expression in AECII cells exposed to LPS. Ultimately, this study revealed the role of the DNMT1/miR-130a/ZEB1 regulatory pathway in AECII cells exposed to LPS. Overall, our data revealed that LPS induced the secretion of inflammatory factors by modulating the DNMT1/miR-130a/ZEB1 regulatory pathway in AECII cells, thus providing a novel theoretical basis that might be beneficial for establishment of diagnostic and therapeutic strategies for sepsis.
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DNMT1/miR-130a/ZEB1调控通路影响脂多糖诱导脓毒症的炎症反应
败血症是影响数百万人的全球性卫生保健问题。DNA甲基转移酶I (DNMT1)介导的DNA甲基化通过影响许多类型的细胞进展事件参与许多人类疾病。然而,DNMT1在脓毒症发展中的作用和潜在的分子机制在很大程度上仍然未知。脂多糖(LPS)诱导脓毒症小鼠模型肺纤维化,与对照组小鼠肺组织相比,脓毒症小鼠模型肺组织中DNMT1表达上调。随后,本研究证实LPS诱导原代II型肺泡上皮细胞(AECII细胞)产生白细胞介素(IL)-7和肿瘤坏死因子(TNF)-α,并促进DNMT1的表达。DNMT1的敲低抑制LPS作用下AECII细胞IL-7和TNF-α的分泌。进一步的研究表明,DNMT1在LPS暴露或不暴露的AECII细胞中抑制miR-130a的表达。接下来,本研究证明miR-130a抑制LPS暴露的AECII细胞中ZEB1的表达。最终,本研究揭示了DNMT1/miR-130a/ZEB1调控通路在LPS作用下AECII细胞中的作用。总之,我们的数据揭示了LPS通过调节AECII细胞的DNMT1/miR-130a/ZEB1调控通路诱导炎症因子的分泌,从而为建立脓毒症的诊断和治疗策略提供了新的理论基础。
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来源期刊
DNA and cell biology
DNA and cell biology 生物-生化与分子生物学
CiteScore
6.60
自引率
0.00%
发文量
93
审稿时长
1.5 months
期刊介绍: DNA and Cell Biology delivers authoritative, peer-reviewed research on all aspects of molecular and cellular biology, with a unique focus on combining mechanistic and clinical studies to drive the field forward. DNA and Cell Biology coverage includes: Gene Structure, Function, and Regulation Gene regulation Molecular mechanisms of cell activation Mechanisms of transcriptional, translational, or epigenetic control of gene expression Molecular Medicine Molecular pathogenesis Genetic approaches to cancer and autoimmune diseases Translational studies in cell and molecular biology Cellular Organelles Autophagy Apoptosis P bodies Peroxisosomes Protein Biosynthesis and Degradation Regulation of protein synthesis Post-translational modifications Control of degradation Cell-Autonomous Inflammation and Host Cell Response to Infection Responses to cytokines and other physiological mediators Evasive pathways of pathogens.
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