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大鼠肝部分切除术后肝细胞的转录组分析。

Transcriptome analysis of hepatocytes after partial hepatectomy in rats.

机构信息

Key Laboratory for Cell Differentiation Regulation, Henan Normal University, 46# East of Construction Road, Xinxiang, 453007, China,

出版信息

Dev Genes Evol. 2010 Dec;220(9-10):263-74. doi: 10.1007/s00427-010-0345-1. Epub 2010 Nov 17.

Abstract

After partial hepatectomy (PH), the recovery of liver mass is mainly mediated by proliferation and enlargement of hepatocytes. Therefore, measuring the transcriptional profiling of hepatocytes after PH will be helpful in exploring the mechanism of liver regeneration (LR). Firstly, hepatocytes were isolated from rat regenerating liver at different time points following PH, and then global gene expression analysis of hepatocytes was performed using Rat Genome 230 2.0 Array. The results demonstrated that 1,417 genes in the array (including 767 known genes) were identified to be LR-related. Clustering analysis demonstrated that 767 known genes fell into six classes with distinct expression kinetics. When gene expression patterns were combined with gene functions, genes involved in acute-phase response and defense response were rapidly elevated in early phases; those in cell proliferation and DNA replication were significantly up-expressed in middle phase; a growing number of cell adhesion-involved genes were up-regulated as regeneration progressed; those in amino acid and lipid metabolism showed persistent down-regulation during LR. Based on the above analyses, it was suggested that hepatocyte defense mechanism was quickly triggered after PH; cell proliferation became active in middle phase; cell adhesion was strengthened in late phase; amino acid and lipid metabolism were attenuated during LR. Additionally, comparative analysis between transcriptional profiling of hepatocytes and regenerating liver indicated a major contribution of hepatocytes to LR.

摘要

肝部分切除(PH)后,肝质量的恢复主要通过肝细胞的增殖和增大来介导。因此,测量 PH 后肝细胞的转录谱对于探索肝再生(LR)的机制将有所帮助。首先,从 PH 后不同时间点的大鼠再生肝中分离出肝细胞,然后使用 Rat Genome 230 2.0 Array 对肝细胞进行全基因表达分析。结果表明,该数组中有 1417 个基因(包括 767 个已知基因)被鉴定为与 LR 相关。聚类分析表明,767 个已知基因分为具有不同表达动力学的六个类别。当基因表达模式与基因功能相结合时,急性期反应和防御反应相关的基因在早期迅速升高;细胞增殖和 DNA 复制相关的基因在中期显著上调;随着再生的进行,越来越多的细胞黏附相关基因上调;氨基酸和脂质代谢相关的基因在 LR 期间持续下调。基于上述分析,提示 PH 后肝细胞防御机制迅速被触发;中期细胞增殖活跃;晚期细胞黏附增强;LR 期间氨基酸和脂质代谢减弱。此外,肝细胞与再生肝转录谱的比较分析表明,肝细胞对 LR 有重要贡献。

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