Differential suppression of liver-specific genes in regenerating rat liver induced by extended hepatectomy
Differential suppression of liver-specific genes in regenerating rat liver induced by extended hepatectomy
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DOI：
10.1016/s0168-8278(00)80226-3
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发表时间：
2000-04-01
影响因子：
25.7
通讯作者：
Yoshida, S
中科院分区：
文献类型：
--
作者：
Kurumiya, Y;Nozawa, K;Yoshida, S
背景/目标：残肝的功能对于扩大肝切除术后患者的生存至关重要，本研究的目的是确定残肝中增殖的肝细胞是否保留肝脏特异性基因的表达。方法：使用30%、70%和90%部分肝切除（PHx）后再生的大鼠肝脏，用7个肝脏特异性基因的探针进行北方印迹分析，结果：在90% PHx后再生过程中，肝脏特异性基因的转录呈现3种时间模式：血清白蛋白和细胞色素P450 2B的转录迅速下降，在PHx后6 ~ 24 h达到最低值;载脂蛋白A-1、磷酸烯醇式丙酮酸羧激酶和鸟氨酸转氨甲酰酶的活性逐渐下降，直至24 ~ 48 h;至PHx后48 h，UDP-葡萄糖醛酸转移酶和肝细胞核因子4均未出现任何变化，相反，所有生长相关基因和管家基因的表达水平在PHx后迅速增加。30和70%PHx后，这些基因的表达以类似的方式改变的90%PHx的情况下，但在较低的程度。结论：基于残余肝脏Ki-67阳性肝细胞的分数，我们可以估计每个肝脏特异性基因的表达程度在增殖的肝细胞。血清白蛋白基因被完全抑制，而编码UDP-葡萄糖醛酸转移酶的基因不受影响。这些结果与PHx后大鼠血清中白蛋白和胆红素的模式相关性良好。其他肝脏特异性基因在增殖的肝细胞中受到中度抑制。因此，当肝细胞进入增殖周期时，肝脏特异性基因的表达受到差异抑制。那些未受影响的可能是必不可少的维持生物体的稳态。
Background/Aims: The function of the remnant liver is critical to survival of patients following an extended hepatectomy, The aim of this study was to determine whether proliferating hepatocytes in the remnant liver preserve the expression of liver-specific genes.Methods: Using regenerating rat livers after 30, 70, and 90% partial hepatectomy (PHx), Northern blot analyses were performed with probes for seven liver-specific genes, six growth-related genes two housekeeping genes and two acute phase reactant protein genes.Results: During the regeneration after 90% PHx, the transcription of liver-specific genes showed three chronological patterns: transcription of serum albumin and cytochrome P450 2B decreased rapidly and reached a nadir at 6 to 24 h after PHx; those of apolipoprotein A-1, phosphoenolpyruvate carboxykinase and ornithine transcarbamylase decreased gradually until 24 to 48 h; those of UDP-glucuronosyltransferase and hepatocyte nuclear factor 4 did not show any changes until 48 h after PHx, In contrast, expression levels of all the growth-related genes and of house-keeping genes increased rapidly after PHx. After 30 and 70% PHx, expression of these genes changed in a similar manner to the 90% PHx case but to a lower extent.Conclusions: Based upon the fractions of Ki-67 positive hepatocytes in remnant livers, we could estimate the degree of expression of each liver-specific gene in the proliferating hepatocytes. The serum albumin gene was completely suppressed, while that encoding UDP-glucuronosyltransferase was not affected. These results correlated well with the patterns of albumin and bilirubin in rat serum after PHx. Other liver-specific genes were moderately suppressed in proliferating hepatocytes. Thus, expression of liver-specific gene is differentially suppressed when hepatocytes enter a proliferation cycle. Those that are unaffected may be indispensable for maintaining the homeostasis of the living organism.