Unveiling the Hub Genes Involved in Cadmium-Induced Hepatotoxicity.

IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Biological Trace Element Research Pub Date : 2025-04-01 Epub Date: 2024-07-16 DOI:10.1007/s12011-024-04307-0
Bing Yang, Zhongyuan Wang, Shujuan Wang, Xiaofeng Li
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Abstract

Cadmium (Cd) is a highly toxic heavy metal that can cause severe liver damage in both humans and animals. However, the specific genes responsible for Cd-induced hepatotoxicity are still not fully understood. Therefore, the aim of this study was to identify the key genes associated with Cd-induced liver damage. To achieve this, we utilized the GSE19662 dataset from the Gene Expression Omnibus (GEO), which consisted of rat hepatocyte samples treated with cadmium chloride (CdCl2) as well as control groups. By focusing on rat hepatocytes treated with 0.10 ppm of CdCl2, the study identified 851 differentially expressed genes (DEGs), with 438 genes being upregulated and 413 genes being downregulated. Gene Ontology (GO) analysis revealed that these DEGs were primarily involved in inflammatory responses, xenobiotic metabolic processes, and the response to drugs and xenobiotic stimuli. Finally, the study identified several hub genes, including CYP2E1, CYP3A62, CYP2C11, CYP2C13, CYP2B3, HSP90B1, HSP90AA1, GSTA2, and MAPK8, which were associated with CdCl2-induced liver damage. Furthermore, pathway analysis demonstrated that these hub genes were mainly linked to pathways involved in chemical carcinogenesis, metabolic processes, steroid hormone biosynthesis, retinol metabolism, linoleic acid metabolism, arachidonic acid metabolism, inflammatory mediator regulation, Ras, and protein processing in the endoplasmic reticulum. In conclusion, this study provides important insights into the molecular mechanisms underlying Cd-induced liver damage.

Abstract Image

揭示参与镉诱导肝中毒的枢纽基因
镉(Cd)是一种剧毒重金属,可对人类和动物的肝脏造成严重损害。然而,导致镉诱导的肝脏毒性的特定基因仍不完全清楚。因此,本研究旨在确定与镉诱导的肝损伤相关的关键基因。为此,我们利用了基因表达总库(Gene Expression Omnibus,GEO)中的 GSE19662 数据集,该数据集包括氯化镉(CdCl2)处理组和对照组的大鼠肝细胞样本。通过聚焦于接受 0.10 ppm 氯化镉处理的大鼠肝细胞,研究发现了 851 个差异表达基因(DEG),其中 438 个基因上调,413 个基因下调。基因本体(GO)分析表明,这些差异表达基因主要参与炎症反应、异种生物代谢过程以及对药物和异种生物刺激的反应。最后,研究发现了几个与氯化镉诱导的肝损伤相关的枢纽基因,包括CYP2E1、CYP3A62、CYP2C11、CYP2C13、CYP2B3、HSP90B1、HSP90AA1、GSTA2和MAPK8。此外,通路分析表明,这些枢纽基因主要与化学致癌、代谢过程、类固醇激素生物合成、视黄醇代谢、亚油酸代谢、花生四烯酸代谢、炎症介质调控、Ras和内质网蛋白加工等通路有关。总之,这项研究为了解镉诱导的肝损伤的分子机制提供了重要见解。
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来源期刊
Biological Trace Element Research
Biological Trace Element Research 生物-内分泌学与代谢
CiteScore
8.70
自引率
10.30%
发文量
459
审稿时长
2 months
期刊介绍: Biological Trace Element Research provides a much-needed central forum for the emergent, interdisciplinary field of research on the biological, environmental, and biomedical roles of trace elements. Rather than confine itself to biochemistry, the journal emphasizes the integrative aspects of trace metal research in all appropriate fields, publishing human and animal nutritional studies devoted to the fundamental chemistry and biochemistry at issue as well as to the elucidation of the relevant aspects of preventive medicine, epidemiology, clinical chemistry, agriculture, endocrinology, animal science, pharmacology, microbiology, toxicology, virology, marine biology, sensory physiology, developmental biology, and related fields.
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