Pathological polyploidy in liver disease.
Pathological polyploidy in liver disease.
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DOI：
10.1002/hep.27908
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发表时间：
2015-09
期刊：
影响因子：
--
通讯作者：
Duncan AW
中科院分区：
文献类型：
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作者：
Hsu SH;Duncan AW
肝脏的组成随着年龄的增长而发生巨大变化。年轻个体的肝细胞相对较小且大小均匀。相比之下，成体肝细胞的细胞和细胞核大小、每个细胞的细胞核数量以及每个细胞核的 DNA 含量差异很大。许多与年龄相关的显着形态变化归因于肝脏多倍体，即整个染色体的数值变化。多倍体肝细胞在一个多世纪前就被认识到，但尚不清楚这些细胞是否在肝脏稳态、再生或疾病中发挥特殊作用。尽管我们对多倍体肝细胞的生理作用了解有限，但近十几个基因与多倍体的调节有关。值得注意的是，尚塔尔·德杜埃茨 (Chantal Desdouets) 的研究小组此前证明了胰岛素在大鼠双核多倍体肝细胞生成中的关键作用。受这些早期发现的启发，Gentric、Celton-Morizur、Desdouets 及其同事合理地认为，经常与胰岛素信号失调相关的肝脏疾病可能具有异常的倍性谱。事实上，在最近的研究中，作者发现了异常肝多倍体与非酒精性脂肪肝 (NAFLD) 之间的联系
The composition of the liver changes dramatically with age. Hepatocytes in young individuals are relatively small and uniform in size. In contrast, adult hepatocytes vary considerably in cell and nuclear size, number of nuclei per cell and DNA content per nucleus. Many of these striking age-associated morphological changes are attributed to hepatic polyploidy, a numerical change in the entire complement of chromosomes. Polyploid hepatocytes were recognized over a century ago, but it is unclear whether these cells play a specialized role in liver homeostasis, regeneration or disease. Despite our limited understanding of the physiological role of polyploid hepatocytes, nearly a dozen genes have been implicated in the regulation of polyploidy. Notably, Chantal Desdouets’ group previously demonstrated a critical role for insulin in the generation of binucleate polyploid hepatocytes in rats. Motivated by these early findings, Gentric, Celton-Morizur, Desdouets and colleagues rationalized that liver diseases frequently associated with dysregulated insulin signaling could have an abnormal ploidy spectrum. Indeed, in recent work the authors identified a connection between abnormal hepatic polyploidy and nonalcoholic fatty liver disease (NAFLD)