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Characterization of transcriptional profiling of Kupffer cells during liver regeneration in rats

机译:大鼠肝再生过程中库普弗细胞转录谱的表征

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KCs (Kupffer cells), as an important hepatic immunoregulatory cells, play a key role in LR (liver regeneration). Uncovering the transcriptional profiling of KCs after PH (partial hepatectomy) would likely clarify its implication in LR. Here, we isolated KCs by methods of Percoll density gradient centrifugation and immunomagnetic beads. Transcriptional profiles of KCs were monitored up to 168 h post-PH using microarray. By comparing the expression profile of KCs at 2-168 h post-PH with that of the control and applying the statistical and bioinformatics criteria, we found 1407 known and 927 unknown genes related to LR. K-means clustering analysis grouped these 1407 genes into robust 14 time-course clusters representing distinct patterns of regulation. Based on gene-set enrichment analysis, genes encoding products involved in cytokine signalling, inflammatory response and cell chaemotaxis were highly enriched in the cluster characterized by gradual up-regulation and then return; genes in defence response and immune response were enriched in clusters 'the general down-regulation during LR'; genes in fatty acid synthesis and sterol metabolism were preferentially distributed in the cluster 'gradual increase'; whereas genes in the categories 'lipid catabolism' and 'glycolysis' were enriched in cluster 'decrease at two intervals'. According to the above analysis, KCs were seemingly sensitive to operative stimulus; immune defence and detoxification function of KCs obviously dropped post-operatively; fatty acid synthesis were enhanced, whereas lipid catabolism and glycolysis were reduced after PH. This study provides a detailed in vivo gene expression profile of KCs, providing a framework to better understand the molecular mechanisms underlying the regeneration process at cellular level.
机译:KCs(库普弗细胞),作为重要的肝脏免疫调节细胞,在LR(肝再生)中起关键作用。 PH(部分肝切除术)后发现KCs的转录谱可能会澄清其在LR中的意义。在这里,我们通过Percoll密度梯度离心和免疫磁珠的方法分离了KC。使用微阵列在PH后168小时内监测KC的转录谱。通过比较PH后2-168 h与对照的KCs表达谱并应用统计学和生物信息学标准,我们发现了1407个与LR相关的已知基因和927个未知基因。 K均值聚类分析将这1407个基因分为14个强大的14个时程簇,分别代表不同的调控模式。根据基因组富集分析,编码涉及细胞因子信号传导,炎症反应和细胞趋血性产物的基因在其特征是逐渐上调然后返回的簇中高度富集。防御反应和免疫反应中的基因富集在“ LR期间的一般下调”簇中;脂肪酸合成和固醇代谢的基因优先分布在“逐渐增加”的簇中;而“脂质分解代谢”和“糖酵解”类别中的基因在簇中“以两个间隔减少”中富集。根据以上分析,KC似乎对手术刺激敏感。术后KCs的免疫防御和解毒功能明显下降; PH后脂肪酸的合成得到增强,而脂质分解代谢和糖酵解减少。这项研究提供了详细的体内KCs基因表达谱,提供了一个框架,可以更好地了解细胞水平上再生过程的分子机制。

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