Changes in albumin, alpha-fetoprotein and collagen gene transcription in CCl4-induced hepatic fibrosis.
Changes in albumin, alpha-fetoprotein and collagen gene transcription in CCl4-induced hepatic fibrosis.
复制标题
CCl4 诱导的肝纤维化中白蛋白、甲胎蛋白和胶原蛋白基因转录的变化。
DOI：
10.1002/hep.1840080212
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Shafritz,DA
中科院分区：
文献类型：
--
作者：
Panduro,A;Shalaby,F;Biempica,L;Shafritz,DA
为了了解肝硬化肝功能障碍的机制，在 CCl 4 诱导的肝纤维化大鼠模型中测量了对肝功能重要的特定基因的转录。研究了纤维化发展过程中和纤维化建立后白蛋白、甲胎蛋白和原α1-胶原蛋白基因的相对转录率。在CCl 4 施用的初始阶段，白蛋白转录减少，且甲胎蛋白转录增加，表明肝再生活跃。然而，在纤维化发展的后期，这些基因的反应模式有所不同，白蛋白基因转录正常或增加，而甲胎蛋白基因转录不再增加。 CCl 4 治疗完成三周后（完全形成肝硬化），白蛋白基因对急性再生刺激反应正常或超正常，但甲胎蛋白基因再次没有可测量的反应。 Pro-α1-胶原蛋白基因转录在整个纤维化过程中增加，并在肝硬化形成后保持升高状态。这些研究表明，从白蛋白到甲胎蛋白基因转录的转变可以作为肝脏再生能力的标志，并且这一过程在肝纤维化发生期间和之后发生改变。纤维形成过程还与胶原蛋白基因转录的升高有关。
In efforts to understand mechanisms of liver dysfunction in cirrhosis, transcription of specific genes important to liver function has been measured in the rat model of CCl 4-induced hepatic fibrosis. The relative transcription rates of albumin, α-fetoprotein and pro-α 1-collagen genes were studied during development of fibrosis and after fibrosis was established. During the initial phase of CCl 4 administration, there was a decrease in albumin transcription associated with increased α-fetoprotein transcription, indicative of active liver regeneration. However, later during development of fibrosis, the response pattern of these genes was different, as albumin gene transcription was normal or increased and α-fetoprotein gene transcription was no longer increased. Three weeks after completion of CCl 4 treatment (fully established cirrhosis), albumin genes responded normally or hypernormally to an acute regenerative stimulus, but the α-fetoprotein gene was again not measurably responsive. Pro-α 1-collagen gene transcription increased during the entire fibrogenic process and remained elevated after cirrhosis was established. These studies suggest that a switch from albumin to α-fetoprotein gene transcription can serve as a marker of liver regenerative capacity, and that this process is altered during and after development of hepatic fibrosis. The fibrogenic process is also associated with elevated transcription of collagen genes.