Epigenetic Regulation of Manganese-Induced Hepatotoxicity Uncovering Histone Demethylation-Associated Gene Networks.

IF 2.8 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-10-01 DOI:10.1002/jbt.70556

Bing Yang, Xiaofeng Li

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引用次数: 0

Abstract

Excessive manganese (Mn) exposure can result in significant liver toxicity in humans and animals. Histone demethylation, a crucial epigenetic modification, is believed to play a pivotal role in liver disease progression. However, the involvement of histone demethylation-associated genes in Mn-induced hepatotoxicity remains poorly understood. This study aimed to identify these genes related to Mn exposure. We analyzed gene expression data, which included liver samples treated with manganese chloride (MnCl₂₎ and control samples. Our analysis revealed 351 differentially expressed genes (DEGs) on Day 3 and 494 DEGs on Day 5 in livers treated with 700 mg/kg MnCl₂. Notably, we identified 24 overlapping histone demethylation-associated DEGs across both time points. Biological process analysis indicated that these DEGs are linked to organ regeneration, cell proliferation, responses to xenobiotic substances and toxins, bile transport, fatty acid metabolism, and posttranscriptional regulation. Pathway analysis identified associations with IL-17 signaling, cAMP pathways, chemical carcinogenesis, and parathyroid hormone synthesis and action. Furthermore, we highlighted several histone demethylation-associated hub genes, including CDKN1A, PPARA, CYP7A1, CAV1, GDF15, and GRP, implicated in Mn-induced hepatotoxicity.

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锰诱导肝毒性的表观遗传调控揭示组蛋白去甲基化相关基因网络。

过量的锰（Mn）暴露可导致人类和动物严重的肝毒性。组蛋白去甲基化是一种重要的表观遗传修饰，被认为在肝脏疾病的进展中起关键作用。然而，组蛋白去甲基化相关基因在锰诱导的肝毒性中的作用仍然知之甚少。本研究旨在鉴定这些与锰暴露相关的基因。我们分析了基因表达数据，其中包括用氯化锰（MnCl2）处理的肝脏样本和对照样本。我们的分析显示，在700 mg/kg MnCl2处理的肝脏中，第3天有351个差异表达基因（DEGs），第5天有494个差异表达基因（DEGs）。值得注意的是，我们在两个时间点上发现了24个重叠的组蛋白去甲基化相关基因。生物过程分析表明，这些deg与器官再生、细胞增殖、对外源物质和毒素的反应、胆汁转运、脂肪酸代谢和转录后调控有关。途径分析确定了与IL-17信号传导、cAMP途径、化学致癌和甲状旁腺激素合成和作用的关联。此外，我们强调了几个组蛋白去甲基化相关的中心基因，包括CDKN1A、PPARA、CYP7A1、CAV1、GDF15和GRP，它们与锰诱导的肝毒性有关。

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

Journal of Biochemical and Molecular Toxicology 生物-毒理学

CiteScore

5.80

自引率

2.80%

发文量

277

审稿时长

6-12 weeks

期刊介绍： The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.