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通过生物信息学分析和实验鉴定部分肝切除术后小鼠肝脏再生中的关键基因

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

作者信息

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

机构信息

Department of Hepatobiliary Surgery, The Affiliated Hospital of Yunnan University, Kunming, China.

Department of Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

出版信息

Front Genet. 2021 Jun 23;12:670706. doi: 10.3389/fgene.2021.670706. eCollection 2021.

Abstract

BACKGROUND

The 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 METHODS

We 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 and .

RESULTS

We 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 .

CONCLUSION

Mouse 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.

摘要

背景

肝脏是唯一能在遭受各种损伤或组织损失后完全再生的器官。肝脏再生中仍有大量基因功能尚未被探索。本研究旨在鉴定部分肝切除(PH)后小鼠肝脏再生早期的关键基因。

材料与方法

我们首先从基因表达综合数据库(GEO)分析了PH后48小时和72小时小鼠肝脏中的基因表达谱。进行基因本体论(GO)、京都基因与基因组百科全书(KEGG)以及蛋白质-蛋白质相互作用(PPI)分析以鉴定肝脏再生中的关键基因。最后,我们验证了关键基因 以及 。

结果

我们分别鉴定出PH后48小时有46个上调基因和19个下调基因,PH后72小时有223个上调基因和40个下调基因。这些基因主要参与细胞周期、DNA复制和p53信号通路。在这些基因中,细胞周期相关基因(Ccna2、Cdkn1a、Chek1和Mcm5)以及Ube2c在PH后48小时和72小时的残余肝脏中均高表达。此外,Ube2c基因敲低不仅导致Ccna2、Cdkn1a、Chek1和Mcm5的异常表达,还抑制肝细胞从细胞周期的G1期向S期转变。

结论

小鼠肝细胞在PH后48小时进入增殖期。Ube2c可能通过调节或部分调节Ccna2、Cdkn1a、Chek1和Mcm5来介导细胞增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/364f/8260846/9dcaf1da70c9/fgene-12-670706-g001.jpg

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