Transcriptional and posttranscriptional effects of dexamethasone on albumin and procollagen messenger RNAs in murine schistosomiasis.
Transcriptional and posttranscriptional effects of dexamethasone on albumin and procollagen messenger RNAs in murine schistosomiasis.
复制标题
地塞米松对鼠血吸虫病白蛋白和前胶原信使 RNA 的转录和转录后影响。
DOI：
10.1021/bi00380a010
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发表时间：
1987
期刊：
影响因子：
2.9
通讯作者：
Zern,MA
中科院分区：
文献类型：
--
作者：
Weiner,FR;Czaja,MJ;Giambrone,MA;Takahashi,S;Biempica,L;Zern,MA
1986年11月21日收到的修订手稿摘要：我们先前已经表明，地塞米松增加了大鼠肝细胞培养中白蛋白的mRNA水平，降低了前胶原的稳态mRNA水平。通过评估体内纤维化模型(小鼠血吸虫病)和确定导致这些变化的更精确的基因表达水平，这些研究得到了扩展。当感染曼氏血吸虫病的小鼠肝脏纤维化且血清白蛋白水平显着降低时，在感染后8周对对照小鼠和同窝小鼠进行评估。在半数感染小鼠的饮用水中加入4Yug/m L的地塞米松，可使肝组织中的胶原含量下降75%。分别在对照组和感染±地塞米松组小鼠肝脏中提取RNA。然后将该RNA与cDNAs探针杂交，以确定特定mRNAs的稳定水平。在感染的小鼠中，白蛋白mRNA的水平与对照组相比降低；然而，地塞米松治疗的感染小鼠在8周时白蛋白mRNA的含量增加了3倍。与对照组相比，感染小鼠的I型和IV型前胶原稳态mRNA水平升高，而地塞米松抑制感染小鼠胶原mRNA水平的50%。通过核连续分析评估了导致这些稳态变化的基因表达水平。血吸虫病对这些基因的影响主要是在转录水平，而地塞米松通过不同的机制作用于受损肝脏中的不同基因，即在转录水平上减少胶原合成，通过转录后机制增加白蛋白。皮质类固醇诱导的改变似乎导致肝功能稳定和抑制纤维化形成。这可能解释了为什么皮质类固醇对人类某些形式的慢性肝病有益。
Revised Manuscript Received November 21, 1986 abstract: We have previously shown that dexamethasone increases albumin mRNA and decreases procollagen steady-state mRNA levels in rat hepatocyte cultures. These studies were extended by evaluating an in vivo model of fibrogenesis (murine schistosomiasis) and by determining a more precise level of gene expression responsible for these changes. Control mice and litter mates infected with Schistosomiasis mansoni were evaluated at 8 weeks postinfection when the livers of the infected mice had become fibrotic and their serum albumin levels significantly decreased. The addition of 4 yug/mL dexamethasone to the drinking water of half of the infected mice led to a 75% decrease in the liver collagen content as determined by highperformance liquid chromatography. RNA was extracted from the livers of mice under three conditions: control and infected±dexamethasone. This RNA was then hybridizedwith cDNA probes to determine steady-state levels of specific mRNAs. In the infected mice, albumin mRNA levels were decreased compared to control; however, infected mice treated with dexamethasone increased their albumin mRNA content by 3-fold at 8 weeks. Types I and IV procollagen steady-state mRNA levels in infected mice were increased compared to control while dexamethasone suppressed the mRNA level of collagen in infected mice by 50%. The level of gene expression responsible for these steady-state changes was evaluated by nuclear run-on analysis. While the effect of schistosomiasis on these genes was primarily at a transcriptional level, dexamethasone exerted its effect on different genes in the injured liver by diverse mechanisms, ie, decreasing collagen synthesis at a transcriptional level and increasing albumin by posttranscriptional mechanisms. Corticosteroid-induced changes appear to lead to a stabilization of liver function and inhibition of fibrogenesis. This may explain why corticosteroids are beneficial in some forms of chronic liver disease in man.