College of Bioscience and Biotechnology, Hunan Agricultural University, Changsha, Hunan 410128, China.
Int Immunopharmacol. 2023 Oct;123:110708. doi: 10.1016/j.intimp.2023.110708. Epub 2023 Jul 29.
Non-alcoholic fatty liver disease (NAFLD) has become a significant cause of chronic liver disease in developed countries, as a result of the worldwide trend of obesity and associated metabolic syndrome. Obesity and high-fat diet (HFD) are very common in patients with NAFLD. However, how to screen out key differentially expressed genes (DEGs) is a challenging task. The purpose of this study is to study the screen of key genes and pathways of HFD on the formation process of non-alcoholic fatty liver through network pharmacological analysis.
In this study, 173 genes associated with NAFLD were collected from the Gene Expression Omnibus (GEO) database. To find significant genes and pathways, combine network clustering analysis, topology analysis, and pathway analysis.
The results showed that there were four key signaling pathways related to HFD, including complement cascade, Atorvastatin ADME, Asthma and Aflatoxin activation and detoxification. In addition, we identified six representative key genes, including Ccl5, Tlr2, Cd274, Cxcl10, Cxcl9 and Cd74, and screened three intersecting genes in Mus musculus and Homo sapiens sample, including C3, F2 and C7.
In conclusion, our study constructed the NAFLD gene regulatory network of C57BL/6J mice for the first time and jointly analyzed the Mus musculus samples and Homo sapiens samples. It provides new insights for identifying potential biomarkers and valuable therapeutic clues, and puts forward a new method for web-based research. These findings may provide potential targets for early diagnosis, effective therapy and prognostic markers of NAFLD.
随着肥胖和相关代谢综合征在全球范围内的流行，非酒精性脂肪性肝病（NAFLD）已成为发达国家慢性肝病的重要病因。肥胖和高脂肪饮食（HFD）在 NAFLD 患者中非常常见。然而，如何筛选出关键差异表达基因（DEGs）是一项具有挑战性的任务。本研究旨在通过网络药理学分析研究 HFD 对非酒精性脂肪肝形成过程中关键基因和途径的筛选。
本研究从基因表达综合数据库（GEO）中收集了 173 个与 NAFLD 相关的基因。为了找到显著的基因和途径，我们结合网络聚类分析、拓扑分析和途径分析。
结果表明，与 HFD 相关的有四个关键信号通路，包括补体级联、阿托伐他汀 ADME、哮喘和黄曲霉毒素激活与解毒。此外，我们鉴定了六个代表性的关键基因，包括 Ccl5、Tlr2、Cd274、Cxcl10、Cxcl9 和 Cd74，并在 Mus musculus 和 Homo sapiens 样本中筛选出三个相交基因，包括 C3、F2 和 C7。
总之，本研究首次构建了 C57BL/6J 小鼠的 NAFLD 基因调控网络，并对 Mus musculus 样本和 Homo sapiens 样本进行了联合分析。它为鉴定潜在的生物标志物和有价值的治疗线索提供了新的见解，并为基于网络的研究提出了一种新方法。这些发现可能为 NAFLD 的早期诊断、有效治疗和预后标志物提供潜在的靶点。
