Weighted Gene Coexpression Network Analysis in Mouse Livers following Ischemia-Reperfusion and Extensive Hepatectomy.

Weighted Gene Coexpression Network Analysis in Mouse Livers following Ischemia-Reperfusion and Extensive Hepatectomy.
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缺血再灌注和广泛肝切除后小鼠肝脏的加权基因共表达网络分析

DOI:
10.1155/2021/3897715
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发表时间:
2021
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Liu Q
Liu Q
中科院分区:
其他
文献类型:
--
作者:
Liu W;Shi Y;Cheng T;Jia R;Sun MZ;Liu S;Liu Q

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在小鼠模型中,肝部分切除后肝脏体积的恢复主要是由肝细胞增殖介导的,通常伴有缺血再灌注。肝部分切除术后肝脏中不同表达基因的鉴定有助于更好地理解肝再生(LR)的分子机制,具有临床应用意义。简而言之,研究广泛肝切除术存活小鼠组收集的肝组织中不同的基因表达模式,对于LR而言,将比研究适当肝切除术存活小鼠组收集的肝组织具有重要意义。在本研究中,我们对肝切除85%(7天存活率为20%)和肝切除50%(缺血再灌注条件下7天存活率为100%)小鼠的肝脏标本进行加权基因共表达网络分析(WGCNA),以确定中心候选基因,并利用鉴定出的动态不同表达基因构建自由尺度基因共表达网络。WGCNA结合京都基因与基因组百科全书(KEGG)和基因本体(GO)富集分析,明确了三个基因表达模块的显著重要性:蓝色模块负责细胞凋亡过程,绿松石模块负责脂质代谢,绿色模块负责脂肪酸代谢。WGCNA分析和蛋白-蛋白相互作用(protein-protein interaction, PPI)网络构建表明FAM175B、OGT和PDE3B是上述三个模块中潜在的三个枢纽基因。这项工作可能有助于为今后肝损伤和肝切除术后LR的基础研究和治疗策略提供新的线索。
In mouse models, the recovery of liver volume is mainly mediated by the proliferation of hepatocytes after partial hepatectomy that is commonly accompanied with ischemia-reperfusion. The identification of differently expressed genes in liver following partial hepatectomy benefits the better understanding of the molecular mechanisms during liver regeneration (LR) with appliable clinical significance. Briefly, studying different gene expression patterns in liver tissues collected from the mice group that survived through extensive hepatectomy will be of huge critical importance in LR than those collected from the mice group that survived through appropriate hepatectomy. In this study, we performed the weighted gene coexpression network analysis (WGCNA) to address the central candidate genes and to construct the free-scale gene coexpression networks using the identified dynamic different expressive genes in liver specimens from the mice with 85% hepatectomy (20% for seven-day survial rate) and 50% hepatectomy (100% for seven-day survial rate under ischemia-reperfusion condition compared with the sham group control mice). The WGCNA combined with Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses pinpointed out the apparent distinguished importance of three gene expression modules: the blue module for apoptotic process, the turquoise module for lipid metabolism, and the green module for fatty acid metabolic process in LR following extensive hepatectomy. WGCNA analysis and protein-protein interaction (PPI) network construction highlighted FAM175B, OGT, and PDE3B were the potential three hub genes in the previously mentioned three modules. This work may help to provide new clues to the future fundamental study and treatment strategy for LR following liver injury and hepatectomy.
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