Marhamati Shayan, Ali Zahra, Zargar Amir Mohammad, Mohagheghi Sina
Research Center for Molecular Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Mol Biol Rep. 2025 Jun 30;52(1):658. doi: 10.1007/s11033-025-10780-0.
Liver cirrhosis represents a significant global health burden with diverse etiological factors. The lipopolysaccharide response pathway is critical in liver disease development. This study investigates this pathway in liver cirrhosis associated with various etiologies, including nonalcoholic steatohepatitis, alcohol consumption, viral infections, autoimmune disorders, and cholestatic disorders.
The GSE25097 and GSE54238 microarray datasets were retrieved from the Gene Expression Omnibus (GEO) database using R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the overlapping Differentially Expressed Genes (DEGs). Gene expression was determined by RT-qPCR, and protein expression was determined by Western blot. A total of 499 overlapping DEGs were identified between the two datasets. Then, the GOBP enrichment analysis subsequently discovered the lipopolysaccharide response pathway, highlighting genes such as CD180, LY96, VCAM-1, and CSF2RB. Based on bioinformatics analysis, the expressions of all mentioned genes were elevated in cirrhotic samples. However, experimental results showed an increase only in CD180 gene expression. Our research has shown that the expressions of the LY96, VCAM-1, and CSF2RB genes were elevated only in PSC cirrhosis. The PSC group had an elevation in LY96 protein expression. On the other hand, all the gene expressions significantly decreased in NASH cirrhosis, although only the VCAM-1 protein expression was reduced in NASH cirrhosis.
The response to the lipopolysaccharide pathway has a complicated role in liver disease pathogenesis. While gene expression of pathway components increases in cholangitis-related cirrhosis, it decreases in NASH-associated cirrhosis.
肝硬化是一个重大的全球健康负担，病因多样。脂多糖反应途径在肝脏疾病发展中至关重要。本研究调查了与各种病因相关的肝硬化中的这一途径，包括非酒精性脂肪性肝炎、饮酒、病毒感染、自身免疫性疾病和胆汁淤积性疾病。
使用R软件从基因表达综合数据库（GEO）中检索GSE25097和GSE54238微阵列数据集。对重叠的差异表达基因（DEG）进行基因本体（GO）和京都基因与基因组百科全书（KEGG）通路富集分析。通过RT-qPCR测定基因表达，通过蛋白质印迹法测定蛋白质表达。在两个数据集中共鉴定出499个重叠的DEG。然后，GOBP富集分析随后发现了脂多糖反应途径，突出了如CD180、LY96、VCAM-1和CSF2RB等基因。基于生物信息学分析，所有上述基因的表达在肝硬化样本中均升高。然而，实验结果显示仅CD180基因表达增加。我们的研究表明，LY96、VCAM-1和CSF2RB基因的表达仅在原发性硬化性胆管炎肝硬化中升高。原发性硬化性胆管炎组LY96蛋白表达升高。另一方面，在非酒精性脂肪性肝炎肝硬化中所有基因表达均显著降低，尽管在非酒精性脂肪性肝炎肝硬化中仅VCAM-1蛋白表达降低。
脂多糖途径的反应在肝脏疾病发病机制中具有复杂的作用。虽然途径成分的基因表达在胆管炎相关肝硬化中增加，但在非酒精性脂肪性肝炎相关肝硬化中降低。
