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Comparative Analysis of the Role of ERK1/2 Signaling Pathway in Regulating Cell Proliferation of Rat Liver Regeneration and Rat Acute Hepatic Failure

机译:ERK1 / 2信号通路在调节大鼠肝再生和大鼠急性肝功能衰竭细胞中作用的比较分析

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After injured or partially hepatectomy (PH), hepatocytes could rapidly enter cell cycle to compensate for the loss of liver tissue, which is regulated by lots of signaling pathway, including ERK1/2 signaling pathway. To compare the role of ERK1/2 signaling pathway in PH-induced liver regeneration (LR) with that in carbon tetrachloride-induced acute hepatic failure (AHF) at gene transcription level, Rat Genome 230 2.0 array was used to detect gene expression profiles of above two processes, and bioinformatics and systems biology methods were applied to analyze the physiological activities uncovered by their profiles. The results showed that 165 genes were associated with fourteen paths of ERK1/2 signaling pathway, 161 genes were contained in the array above, and 46 genes were significantly expressed. Of them, 36 genes were the LR-specific genes, 24 genes were the AHF-specific, and 14 genes were the common genes. Synergy value of these genes was calculated using a mathematical model established by our lab, and the results showed that the cell proliferation-promoting effect of path 4 was weaker than the control at 6h of AHF occurrence, while those of paths 2, 8, and 9 at 12h of LR and paths 2 and 6 at 72h of AHF were stronger. On the other hand, the cell proliferation-inhibiting effect of path 11 was stronger at 12h of LR and AHF, but that of path 13 was weaker at 24h of LR. In conclusion, 46 genes related to seven paths of ERK1/2 signaling pathway regulates cell proliferation in both LR and AHF.
机译:受伤或部分切除肝(PH)后,肝细胞可以迅速进入细胞周期以补偿肝组织的损失,肝组织的损失受到许多信号通路(包括ERK1 / 2信号通路)的调节。为了在基因转录水平上比较ERK1 / 2信号通路在PH诱导的肝再生(LR)和四氯化碳诱导的急性肝衰竭(AHF)中的作用,使用Rat Genome 230 2.0阵列检测ERK1 / 2信号通路以上两个过程,并应用生物信息学和系统生物学方法来分析其概况所揭示的生理活动。结果表明,有165个基因与ERK1 / 2信号通路的14个路径相关,上面的阵列中包含161个基因,并且有46个基因被显着表达。其中,LR特异性基因有36个基因,AHF特异性基因有24个基因,共同基因有14个基因。使用我们实验室建立的数学模型计算这些基因的协同价值,结果表明,在AHF发生6h时,路径4的细胞增殖促进作用比对照弱,而路径2、8和8的细胞增殖促进作用弱于对照组。 LR 12h处的9号和AHF 72h处的路径2和6较强。另一方面,路径11的细胞增殖抑制作用在LR和AHF的12h时较强,但是路径13的强度在LR的24h时较弱。总之,与ERK1 / 2信号通路的七个通路相关的46个基因调节LR和AHF中的细胞增殖。

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