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通过生物相互作用网络分析动脉粥样硬化与非酒精性脂肪肝疾病的遗传关系。

Analysis of the Genetic Relationship between Atherosclerosis and Non-Alcoholic Fatty Liver Disease through Biological Interaction Networks.

机构信息

Instituto de Investigación Biosanitaria de Granada (ibs. GRANADA), 18014 Granada, Spain.

CIBER on Frailty and Healthy Aging (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain.

出版信息

Int J Mol Sci. 2023 Feb 18;24(4):4124. doi: 10.3390/ijms24044124.

Abstract

Non-alcoholic fatty liver disease (NAFLD) seems to have some molecular links with atherosclerosis (ATH); however, the molecular pathways which connect both pathologies remain unexplored to date. The identification of common factors is of great interest to explore some therapeutic strategies to improve the outcomes for those affected patients. Differentially expressed genes (DEGs) for NAFLD and ATH were extracted from the GSE89632 and GSE100927 datasets, and common up- and downregulated DEGs were identified. Subsequently, a protein-protein interaction (PPI) network based on the common DEGs was performed. Functional modules were identified, and the hub genes were extracted. Then, a Gene Ontology (GO) and pathway analysis of common DEGs was performed. DEGs analysis in NAFLD and ATH showed 21 genes that were regulated similarly in both pathologies. The common DEGs with high centrality scores were ADAMTS1 and CEBPA which appeared to be down- and up-regulated in both disorders, respectively. For the analysis of functional modules, two modules were identified. The first one was oriented to post-translational protein modification, where ADAMTS1 and ADAMTS4 were identified, and the second one mainly related to the immune response, where CSF3 was identified. These factors could be key proteins with an important role in the NAFLD/ATH axis.

摘要

非酒精性脂肪性肝病 (NAFLD) 似乎与动脉粥样硬化 (ATH) 有一些分子联系;然而,将这两种病理联系起来的分子途径至今仍未被探索。鉴定共同的因素对于探索一些治疗策略以改善受影响患者的预后非常重要。从 GSE89632 和 GSE100927 数据集提取了用于 NAFLD 和 ATH 的差异表达基因 (DEGs),并鉴定了常见的上调和下调 DEGs。随后,基于共同 DEGs 进行了蛋白质-蛋白质相互作用 (PPI) 网络分析。识别功能模块,并提取枢纽基因。然后,对共同 DEGs 进行了基因本体论 (GO) 和通路分析。NAFLD 和 ATH 的 DEGs 分析显示,在两种疾病中均受到调节的 21 个基因。具有高中心性评分的共同 DEGs 是 ADAMTS1 和 CEBPA,它们分别在两种疾病中表现为下调和上调。对于功能模块的分析,鉴定了两个模块。第一个模块定向于翻译后蛋白修饰,其中鉴定了 ADAMTS1 和 ADAMTS4,第二个模块主要与免疫反应相关,其中鉴定了 CSF3。这些因素可能是在 NAFLD/ATH 轴中具有重要作用的关键蛋白。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/50fb/9966194/c4d9cf3468be/ijms-24-04124-g001.jpg

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