Elevation and characteristics of Rab30 and S100a8/S100a9 expression in an early phase of liver regeneration in the mouse
Elevation and characteristics of Rab30 and S100a8/S100a9 expression in an early phase of liver regeneration in the mouse
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DOI：
10.3892/ijmm.2011.614
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发表时间：
2011-04-01
影响因子：
5.4
通讯作者：
Ohkohchi, Nobuhiro
中科院分区：
文献类型：
--
作者：
Chiba, Mitsuru;Murata, Soichiro;Ohkohchi, Nobuhiro
最近的研究表明，包括TNF α和IL-6在内的细胞因子在肝脏再生的启动阶段起着关键作用。然而，需要进一步了解启动阶段的分子事件，以便更全面地了解肝脏再生的启动。在目前的研究中，我们试图确定在早期阶段（肝部分切除术后2-6小时）参与的其他基因。使用微阵列分析显示，与正常肝脏相比，在PH后2小时和6小时，肝脏中71个基因的表达上调了3倍以上。其中Rab30和S100a8/S100a9在PH后2 h被鉴定为与正常肝脏相比上调20倍以上的新基因，并通过RT-qPCR进一步检测芯片结果。与假手术小鼠相比，在PH后6 h， Rab30在除肝脏外的其他器官中无显著上调，而S100a8/S100a9在肺和脾脏等其他器官中均有显著上调，表明Rab30与S100a8/S100a9之间存在不同的上调机制。在不同发育阶段的肝脏中进一步研究了它们的表达。Rab30仅在新生儿肝脏中表达，而S100a8/S100a9在胚胎期高表达，且在新生儿肝脏中表达水平最高。这些发现提示Rab30和S100a8/S100a9可能参与了新生儿阶段肝脏从造血支持到代谢的功能转换，但在肝脏发育过程中可能发挥不同的作用。综上所述，Rab30和S100a8/S100a9可能参与了新生儿肝脏再生的启动，并可能参与了肝脏功能的转换。
Recent studies have revealed that cytokines, including TNF alpha and IL-6 play key roles in the priming phase of liver regeneration. However, further knowledge of molecular events in the priming phase is needed for more comprehensively understanding the initiation of liver regeneration. In the present study, we attempted to identify additional genes involved in an early phase (2-6 h post partial hepatectomy, PH). The expression of 71 genes was shown to be up-regulated more than 3-fold in the liver at 2 h and 6 h post PH, as compared to 0 h (normal livers) using microarray analysis. Among them, Rab30 and S100a8/S100a9, were identified as novel genes up-regulated over 20-fold at 2 h post PH as compared to normal liver, and were further examined by RT-qPCR to confirm microarray results. Rab30 showed no significant up-regulation in organs other than the liver, whereas S100a8/S100a9 showed significant up-regulation in other organs, such as the lung and spleen at 6 h post PH as compared to those of sham-operated mice, indicating the existence of a different up-regulation machinery between Rab30 and S100a8/S100a9. Their expression was further investigated in the liver at various developmental stages. Rab30 was shown to be expressed only in newborn liver, whereas S100a8/S100a9 was highly expressed in embryo stages, and exhibited the highest levels in newborn liver. These findings imply that Rab30 and S100a8/S100a9 are possibly involved in the functional switch from hematopoiesis support to metabolism in the newborn stage, but might play different roles in liver development. In conclusion, Rab30 and S100a8/S100a9 were indicated to play roles in the initiation of liver regeneration as well as possibly in the functional switch of the liver in the newborn stage.