Polyploidy and liver proliferation Central role of insulin signaling
Polyploidy and liver proliferation Central role of insulin signaling
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DOI：
10.4161/cc.9.3.10542
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发表时间：
2010-02-01
期刊：
影响因子：
4.3
通讯作者：
Desdouets, Chantal
中科院分区：
文献类型：
--
作者：
Celton-Morizur, Severine;Merlen, Gregory;Desdouets, Chantal
多倍体细胞的形成是几种组织发育程序的一部分。多倍体是哺乳动物肝细胞的特征，目前认为这一过程是限制肝脏生长的重要机制。我们以前曾证明，在出生后发育过程中，由于胞质分裂失败，会出现双核四倍体肝细胞。这种双核四倍体细胞的产生是建立肝脏多倍体的关键步骤。我们最近的工作确定了控制这一过程的细胞信号通路。循环胰岛素水平低的大鼠双核四倍体肝细胞的形成减少，而注射胰岛素的大鼠双核四倍体肝细胞的形成增加。此外，Akt活性的调节明显控制细胞质分裂失败事件，这表明位于胰岛素信号下游的PI3K-Akt通路是四倍化过程的中心。在这里，我们在细胞如何在生理或病理生长过程中成为多倍体的背景下讨论这些发现。
The formation of polyploid cells is part of the developmental program in several tissues. Polyploidy is a characteristic feature of mammalian hepatocytes and it is emerging that this process is an important mechanism of restricting liver growth. We previously demonstrated that during post-natal development, binucleated tetraploid hepatocytes arise due to a failure in cytokinesis. The genesis of such binucleated tetraploid cells is the crucial step for the establishment of liver polyploidization. Our recent work identified the cellular signaling pathway controlling this process. Rats with low levels of circulating insulin exhibit reduced formation of binucleated tetraploid hepatocytes, whereas rats injected with insulin exhibit increased formation of binucleated tetraploid hepatocytes. Furthermore, modulation of Akt activity clearly controls cytokinesis failure events indicating that the PI3K-Akt pathway, downstream from the insulin signal, is central to tetraploidization process. Here, we discuss these findings in the context of how cells become polyploid during physiological or pathological growth.