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

Abstract

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.

Integrated analysis of lncRNA/circRNA–miRNA–mRNA in the proliferative phase of liver regeneration in mice with liver fibrosis

“…MEturquoise (0 h) and MEblue (12 h) had the highest correlations with fibrotic liver regeneration, suggesting that the expression of hub genes exhibited the most significant changes in the early stage of liver regeneration. Using an ischemia-reperfusion 85% hepatectomy mouse model and mRNA microarray analysis, Liu et al [38] performed WGCNA and showed that the changes of hub gene expression were most significant during 6-24 h after hepatectomy. Furthermore, Zhu [39] conducted WGCNA based on a rat portal vein ligation model and transcriptome-wide sequencing and revealed that the changes in hub gene expression were most significant at 0 h after operation.…”