Identification of pivotal genes and crucial pathways in liver fibrosis through WGCNA analysis.

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY Accounts of Chemical Research Pub Date : 2024-07-30 DOI:10.3233/THC-241142

Xibing Zhang, Fuli Yang, Lei Han, Qiuming Su, Yang Gao, Ruichao Wu, Duo Wang, Wang Li, Kepu Zheng, Fang Liu, Jianghua Ran

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Abstract

Background: Liver fibrosis is a progressive liver disease with increasing incidence, yet its underlying pathogenic mechanisms remain incompletely understood.

Objective: : This study aims to explore potential therapeutic targets for liver fibrosis using weighted gene co-expression network analysis (WGCNA) and experimental validation.

Methods: We retrieved the microarray data (GSE174099) from the GEO database and performed differential expression analysis and WGCNA to identify co-expression modules associated with liver fibrosis. A module with the highest correlation to liver fibrosis was selected for further analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to investigate the biological functions and signaling pathways of the identified genes. Protein-protein interaction (PPI) networks were constructed using the STRING database. The correlation between core genes and immune cells was analyzed with the CIBERSORT algorithm. Additionally, pathological and molecular biology experiments were performed to validate the expression levels of core genes in liver tissue, including HE and Masson staining, immunohistochemistry, RT-qPCR, and Western blotting.

Results: We identified a total of 86 intersecting genes from the differential expression analysis and WGCNA. GO enrichment analysis revealed that these genes were involved in processes such as cellular response to cAMP, collagen-containing extracellular matrix, and G protein-coupled receptor binding. KEGG pathway analysis highlighted the involvement of these genes in pathways like Cell Adhesion Molecules and the PI3K-Akt signaling pathway. Using Cytoscape software, we identified four core genes: Cftr, Cldn4, Map2, and Spp1. Pathological examinations showed that the experimental group exhibited significant fibrous tissue proliferation compared to the control group. Immunohistochemistry, RT-qPCR, and Western blotting analyses confirmed that these core genes were significantly upregulated in the experimental group (P< 0.05).

Conclusion: This study identified four key genes (Cftr, Cldn4, Map2, Spp1) that are significantly associated with liver fibrosis. These genes are upregulated in liver fibrosis and could potentially as biomarkers for diagnosis and targets for therapeutic interventions.

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通过 WGCNA 分析鉴定肝纤维化的关键基因和重要通路。

背景：肝纤维化是一种进展性肝病，发病率越来越高，但其潜在的致病机制仍不完全清楚：本研究旨在通过加权基因共表达网络分析（WGCNA）和实验验证，探索肝纤维化的潜在治疗靶点：我们从 GEO 数据库中检索了微阵列数据（GSE174099），并进行了差异表达分析和 WGCNA，以确定与肝纤维化相关的共表达模块。我们选择了一个与肝纤维化相关性最高的模块作进一步分析。基因本体（GO）和京都基因组百科全书（KEGG）通路富集分析用于研究已识别基因的生物学功能和信号通路。利用 STRING 数据库构建了蛋白质-蛋白质相互作用（PPI）网络。利用 CIBERSORT 算法分析了核心基因与免疫细胞之间的相关性。此外，为了验证核心基因在肝组织中的表达水平，还进行了病理和分子生物学实验，包括 HE 和 Masson 染色、免疫组化、RT-qPCR 和 Western 印迹：结果：通过差异表达分析和 WGCNA，我们共发现了 86 个交叉基因。GO富集分析显示，这些基因参与了细胞对cAMP的反应、含胶原的细胞外基质和G蛋白偶联受体结合等过程。KEGG 通路分析显示，这些基因参与了细胞粘附分子和 PI3K-Akt 信号通路等通路。利用 Cytoscape 软件，我们确定了四个核心基因：Cftr、Cldn4、Map2 和 Spp1。病理检查显示，与对照组相比，实验组表现出明显的纤维组织增生。免疫组化、RT-qPCR 和 Western 印迹分析证实，这些核心基因在实验组中显著上调（P< 0.05）：本研究发现了与肝纤维化密切相关的四个关键基因（Cftr、Cldn4、Map2、Spp1）。这些基因在肝纤维化中上调，有可能成为诊断的生物标志物和治疗干预的靶点。

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

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.

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