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Study on the activity of the signaling pathways regulating hepatocytes from G0 phase into G1 phase during rat liver regeneration

机译:大鼠肝再生过程中从G0期到G1期调节肝细胞信号通路活性的研究

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摘要

Under normal physiological conditions, the majority of hepatocytes are in the functional state (G0 phase). After injury or liver partial hepatectomy (PH), hepatocytes are rapidly activated to divide. To understand the mechanism underlying hepatocyte G0/G1 transition during rat liver regeneration, we used the Rat Genome 230 2.0 Array to determine the expression changes of genes, then searched the GO and NCBI databases for genes associated with the G0/G1 transition, and QIAGEN and KEGG databases for the G0/G1 transition signaling pathways. We used expression profile function (E t) to calculate the activity level of the known G0/G1 transition signal pathways, and Ingenuity Pathway Analysis 9.0 (IPA) to determine the interactions among these signaling pathways. The results of our study show that the activity of the signaling pathways of HGF, IL-10 mediated by p38MAPK, IL-6 mediated by STAT3, and JAK/STAT mediated by Ras/ERK and STAT3 are significantly increased during the priming phase (2–6 h after PH) of rat liver regeneration. This leads us to conclude that during rat liver regeneration, the HGF, IL-10, IL-6 and JAK/STAT signaling pathways play a major role in promoting hepatocyte G0/G1 transition in the regenerating liver.
机译:在正常生理条件下,大多数肝细胞处于功能状态(G0期)。受伤或肝部分切除后(PH),肝细胞迅速活化分裂。为了了解大鼠肝再生过程中肝细胞G0 / G1转变的潜在机制,我们使用大鼠基因组230 2.0阵列确定基因的表达变化,然后在GO和NCBI数据库中搜索与G0 / G1转变相关的基因,以及QIAGEN和KEGG数据库以获取G0 / G1过渡信号通路。我们使用表达谱功能(E t)来计算已知的G0 / G1过渡信号途径的活性水平,并使用“独创性途径分析9.0”(IPA)确定这些信号途径之间的相互作用。我们的研究结果表明,在启动阶段,HGF,p38MAPK介导的IL-10,STAT3介导的IL-6以及Ras / ERK和STAT3介导的JAK / STAT的信号通路活性显着增加(2 PH)–大鼠肝脏再生后–6 h。这使我们得出结论,在大鼠肝再生过程中,HGF,IL-10,IL-6和JAK / STAT信号通路在促进再生肝中肝细胞G0 / G1过渡中起主要作用。

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