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.

Highlights

  • Partial hepatectomy is a routine surgical procedure in liver resection, trauma, and transplantation

  • We explored an 85% of hepatectomy in mice and aimed to investigate the molecular mechanisms and provide a theoretical basis to expand surgical hepatectomy ratio. e weighted gene coexpression network analysis (WGCNA), a highly effective method for the construction of coexpression networks by using large-scale datasets and for the rapid identification of genes with close associations in functions [7], was performed in current work. e relevant gene modules and hub genes in important biological processes were extensively explored using WGCNA in the combination with Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses related to liver regeneration. e differentially expressed genes (DEGs) together with their potential interaction mechanisms raveled in current work provide new clues to the future fundamental study and treatment strategy for LR following liver injury and hepatectomy

  • Before the construction of the weighted coexpression network, a weighted parameter of the adjacency function was selected to build the scale-free networks as shown in Figures 3(a) and 3(b). e data demonstrated that the closer was for the branches, and the more similar was for their expression profiles

Read more

Summary

Introduction

Partial hepatectomy is a routine surgical procedure in liver resection, trauma, and transplantation. Liver ischemiareperfusion injury commonly happens as one of the main causes of acute liver dysfunction and failure after partial hepatectomy and liver transplantation [1, 2]. The precise mechanisms underlying ischemia-reperfusion injury have been poorly elucidated. Partial hepatectomy and ischemia-reperfusion trigger hypovolemic shock in liver as an inevitable complication and a significant challenge for clinical management [4]. E investigation on the gene expression alterations with the underlying molecular mechanisms in ischemia-reperfusion injury helps us to manage and control iatrogenic liver damage and dysfunction. Partial (two-thirds) hepatectomy is used to resect diseased livers [5], while a larger proportion of liver resection is required for liver donation. The progress on liver regeneration (LR) already made the successful treatments of liver cancer and liver cirrhosis with extensive hepatectomy and the feasibility of liver

Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call