Liver maturation deficiency in p57Kip2-/- mice occurs in a hepatocytic p57Kip2 expression-independent manner.
Liver maturation deficiency in p57Kip2-/- mice occurs in a hepatocytic p57Kip2 expression-independent manner.
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p57Kip2-/- 小鼠的肝脏成熟缺陷以肝细胞 p57Kip2 表达独立的方式发生。
DOI：
10.1016/j.ydbio.2015.07.004
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Kamiya A.
中科院分区：
文献类型：
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作者：
agida A;Chikada H;Ito K;Umino A;Kato-Itoh M;Yamazaki Y;Sato H;Kobayashi T;Yamaguchi T;Nakayama KI;Nakauchi H;Kamiya A.
胎肝干/祖细胞，即成肝细胞，是高度增殖的细胞，是肝细胞和胆管细胞的来源。相反，成熟肝细胞具有低增殖能力和高代谢功能。细胞增殖受细胞周期相关分子调控。然而，细胞周期调控与肝脏成熟之间的关系仍然是未知的。为了解决这个问题，我们揭示了细胞周期抑制剂p57 Kip 2在胎肝的成肝细胞和间充质细胞中以时空方式表达。此外，我们发现，与野生型（WT）小鼠相比，p57 Kip 2 −/−小鼠的肝母细胞高度增殖，成熟不足。然而，除了Ccnd 2外，细胞周期和双能性相关基因的表达水平没有显着差异。此外，在p57 Kip 2 −/−和WT嵌合小鼠中，p57 Kip 2 −/−肝母细胞可以分化为成熟的肝细胞，这表明p57 Kip 2的内在活性并不简单地调节肝母细胞的成熟。
Fetal hepatic stem/progenitor cells, hepatoblasts, are highly proliferative cells and the source of both hepatocytes and cholangiocytes. In contrast, mature hepatocytes have a low proliferative potency and high metabolic functions. Cell proliferation is regulated by cell cycle-related molecules. However, the correlation between cell cycle regulation and hepatic maturation are still unknown. To address this issue, we revealed that the cell cycle inhibitor p57Kip2was expressed in the hepatoblasts and mesenchymal cells of fetal liver in a spatiotemporal manner. In addition, we found that hepatoblasts inp57Kip2−/− mice were highly proliferative and had deficient maturation compared with those in wild-type (WT) mice. However, there were no remarkable differences in the expression levels of cell cycle- and bipotency-related genes except forCcnd2. Furthermore,p57Kip2−/− hepatoblasts could differentiate into mature hepatocytes inp57Kip2−/− and WT chimeric mice, suggesting that the intrinsic activity of p57Kip2does not simply regulate hepatoblast maturation.