Identifying the Key Genes in Mouse Liver Regeneration After Partial Hepatectomy by Bioinformatics Analysis and in vitro/vivo Experiments.

Jian Zhao,Shi-Zhe Yu,Ling-Peng Yang,Qiang Cai,Long Jiang,Duo Ma,Zhi-Yong Yu

doi:10.3389/fgene.2021.670706

Jian Zhao, Shi-Zhe Yu + Show 5 more

Open Access

https://doi.org/10.3389/fgene.2021.670706

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Abstract

BackgroundThe liver is the only organ that can completely regenerate after various injuries or tissue loss. There are still a large number of gene functions in liver regeneration that have not been explored. This study aimed to identify key genes in the early stage of liver regeneration in mice after partial hepatectomy (PH).Materials and MethodsWe first analyzed the expression profiles of genes in mouse liver at 48 and 72 h after PH from Gene Expression Omnibus (GEO) database. Gene ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) analysis were performed to identify key genes in liver regeneration. Finally, we validated key genes in vivo and in vitro.ResultsWe identified 46 upregulated genes and 19 downregulated genes at 48 h after PH, and 223 upregulated genes and 40 downregulated genes at 72 h after PH, respectively. These genes were mainly involved in cell cycle, DNA replication, and p53 signaling pathway. Among of these genes, cycle-related genes (Ccna2, Cdkn1a, Chek1, and Mcm5) and Ube2c were highly expressed in the residual liver both at 48 and 72 h after PH. Furthermore, Ube2c knockdown not only caused abnormal expression of Ccna2, Cdkn1a, Chek1, and Mcm5, but also inhibited transition of hepatocytes from G1 to S phase of the cell cycle in vitro.ConclusionMouse hepatocytes enter the proliferation phase at 48 h after PH. Ube2c may mediate cell proliferation by regulating or partially regulating Ccna2, Cdkn1a, Chek1, and Mcm5.

Highlights

As an important organ for energy metabolism, bile production, and detoxification, liver is the only organ that can completely regenerate through liver cell mitosis and proliferation (Fausto et al, 2006; Song et al, 2021)
We got a total of 46 upregulated genes and 19 downregulated genes
In biological pathways (BP) term, the result demonstrated that these upregulated genes were mainly enriched in cell cycle, cell division, mitotic nuclear division; In cell components (CC) term, these upregulated genes were mainly involved in nucleus, cytoplasm, nucleoplasm; In molecular functions (MF) term, these upregulated genes were mainly associated with protein binding, ATP binding and nucleotide binding (Figure 2C)

Summary

Introduction

As an important organ for energy metabolism, bile production, and detoxification, liver is the only organ that can completely regenerate through liver cell mitosis and proliferation (Fausto et al, 2006; Song et al, 2021). This allows partial hepatectomy (PH) without affecting liver function when treating liver diseases such as primary or secondary liver tumors (Alkhalili and Berber, 2014). Studies have shown that coagulation, cytokines and growth factors secreted by inflammatory cells are the major stimulators for liver regeneration (Karin and Clevers, 2016; Isfordink et al, 2017). This study aimed to identify key genes in the early stage of liver regeneration in mice after partial hepatectomy (PH)

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