Overexpression of the IGF2-mRNA binding protein p62 in transgenic mice induces a steatotic phenotype.
Overexpression of the IGF2-mRNA binding protein p62 in transgenic mice induces a steatotic phenotype.
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DOI：
10.1016/j.jhep.2010.08.034
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发表时间：
2011-05
影响因子：
25.7
通讯作者：
Kiemer AK
中科院分区：
文献类型：
--
作者：
Tybl E;Shi FD;Kessler SM;Tierling S;Walter J;Bohle RM;Wieland S;Zhang J;Tan EM;Kiemer AK
胰岛素样生长因子2（IGF 2）mRNA结合蛋白p62在肝细胞癌组织中高表达。尽管如此，它在肝脏疾病中的潜在作用在很大程度上是未知的。在这项研究中，我们研究了p62过表达的病理生理意义的小鼠。 我们在LAP启动子下产生过表达p62的小鼠。通过实时荧光定量PCR检测mRNA表达水平和稳定性。在将小鼠与SD 7动物杂交后评估Igf2和H19的等位基因特异性表达。Western Blot法检测Igf2下游介导因子pAKT和PTEN的表达。肝脏p62过度表达既不诱导炎症过程，也不诱导肝损伤。然而，2.5周龄的转基因动物显示脂肪变性表型和改善的葡萄糖耐量。p62过表达诱导印迹基因Igf2和H19及其转录调节因子Aire（自身免疫调节因子）的表达。Igf2和H19的单等位基因表达和mRNA稳定性均不受影响。研究Igf2下游信号传导途径显示AKT活化增加和PTEN表达减弱。脂肪变性表型的诱导意味着p62在肝脏病理生理学中起作用。
The insulin-like growth-factor 2 (IGF2) mRNA binding protein p62 is highly expressed in hepatocellular carcinoma tissue. Still, its potential role in liver disease is largely unknown. In this study we investigated pathophysiological implications of p62 overexpression in mice. We generated mice overexpressing p62 under an LAP-promotor. mRNA expression levels and stability were examined by real-time RT-PCR. Allele-specific expression of Igf2 and H19 were assessed after crossing mice with SD7 animals. The Igf2 downstream mediators pAKT and PTEN were determined by Western Blot. Hepatic p62 overexpression did neither induce inflammatory processes or liver damage. However, 2.5 week old transgenic animals displayed a steatotic phenotype and improved glucose tolerance. p62 overexpression induced the expression of the imprinted genes Igf2 and H19 and their transcriptional regulator Aire (autoimmune regulator). Neither monoallelic expression nor mRNA stability of Igf2 and H19 was affected. Investigating Igf2 downstream signalling pathways showed increased AKT activation and attenuated PTEN expression. The induction of a steatotic phenotype implies that p62 plays a role in hepatic pathophysiology.
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影响因子：
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