Table_2_Selenotranscriptome Network in Non-alcoholic Fatty Liver Disease.xlsx

Observational studies indicate that selenium may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Transcriptomic exploration of the aetiology and progression of NAFLD may offer insight into the role selenium plays in this disease. This study compared gene expression levels of known selenoprotein pathways between individuals with a healthy liver to those with NAFLD. Publicly available gene expression databases were searched for studies that measured global gene expression in liver samples from patients with steatosis and non-alcoholic steatohepatitis (NASH) and healthy controls (with [HOC] or without [HC] obesity). A subset of five selenoprotein-related pathways (164 genes) were assessed in the four datasets included in this analysis. The gene TXNRD3 was less expressed in both disease groups when compared with HOC. SCLY and SELENOO were less expressed in NASH when compared with HC. SELENOM, DIO1, GPX2, and GPX3 were highly expressed in NASH when compared to HOC. Disease groups had lower expression of iron-associated transporters and higher expression of ferritin-encoding sub-units, consistent with dysregulation of iron metabolism often observed in NAFLD. Our bioinformatics analysis suggests that the NAFLD liver may have lower selenium levels than a disease-free liver, which may be associated with a disrupted iron metabolism. Our findings indicate that gene expression variation may be associated with the progressive risk of NAFLD.

观察性研究表明，硒（selenium）可能参与非酒精性脂肪性肝病（non-alcoholic fatty liver disease, NAFLD）的发病机制。针对NAFLD病因与进展的转录组学探索，或可揭示硒在该疾病中的作用。本研究对比了健康人群与NAFLD患者体内已知硒蛋白通路（selenoprotein pathways）的基因表达水平。我们检索了公开可用的基因表达数据库，筛选以脂肪变性（steatosis）患者、非酒精性脂肪性肝炎（non-alcoholic steatohepatitis, NASH）患者的肝脏样本，以及健康对照样本（分为伴肥胖健康对照[HOC]与不伴肥胖健康对照[HC]）为对象的全基因表达检测研究。本分析纳入4个数据集，对其中5个硒蛋白相关通路（共计164个基因）进行了评估。相较于伴肥胖健康对照（HOC），两个疾病组的硫氧还蛋白还原酶3（TXNRD3）基因表达水平均显著降低；与不伴肥胖健康对照（HC）相比，NASH组的半胱氨酸裂解酶（SCLY）与硒蛋白O（SELENOO）表达水平更低。相较于HOC，NASH组的硒蛋白M（SELENOM）、脱碘酶1（DIO1）、谷胱甘肽过氧化物酶2（GPX2）及谷胱甘肽过氧化物酶3（GPX3）表达水平显著升高。疾病组的铁相关转运蛋白表达量更低，而铁蛋白编码亚基表达量更高，这与NAFLD中常见的铁代谢紊乱表现一致。本研究的生物信息学分析结果显示，NAFLD患者的肝脏硒水平可能低于健康肝脏，这或与铁代谢紊乱存在关联。本研究结果表明，基因表达变异可能与NAFLD的进展风险相关。