Nrf2 is involved in maintaining hepatocyte identity during liver regeneration.
Nrf2 is involved in maintaining hepatocyte identity during liver regeneration.
复制标题
DOI：
10.1371/journal.pone.0107423
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Dai G
中科院分区：
文献类型：
--
作者：
Zou Y;Lee J;Nambiar SM;Hu M;Rui W;Bao Q;Chan JY;Dai G
Nrf2 是细胞防御氧化应激和炎症的核心调节因子，参与肝脏再生过程中肝细胞增殖的调节。然而，目前尚不清楚 Nrf2 是否调节肝细胞生长，肝细胞生长是部分肝切除术 (PH) 后恢复失去的肝脏质量的重要细胞机制。为了确定这一点，在 PH 后对野生型和 Nrf2 缺失小鼠进行了各种分析。我们发现，PH后60小时，绝大多数缺乏Nrf2的肝细胞尺寸减小，激活肝祖细胞标记物（CD133、TWEAK受体和三叶因子家族3），耗尽HNF4α蛋白，并下调一组对其功能至关重要的基因的表达。因此，Nrf2 缺陷肝细胞的特性因肝脏质量损失而短暂但严重受损。该事件与肝 HNF4α（肝细胞分化的主要调节因子）的蛋白质消耗以及关键肝细胞生长信号分子肝 Akt1 和 p70S6K 的同时失活有关。我们得出的结论是，Nrf2 通过确保肝再生过程中 HNF4α、Akt1 和 p70S6K 的适当调节，参与维持新再生的肝细胞处于完全分化状态。
Nrf2, a central regulator of the cellular defense against oxidative stress and inflammation, participates in modulating hepatocyte proliferation during liver regeneration. It is not clear, however, whether Nrf2 regulates hepatocyte growth, an important cellular mechanism to regain the lost liver mass after partial hepatectomy (PH). To determine this, various analyses were performed in wild-type and Nrf2-null mice following PH. We found that, at 60 h post-PH, the vast majority of hepatocytes lacking Nrf2 reduced their sizes, activated hepatic progenitor markers (CD133, TWEAK receptor, and trefoil factor family 3), depleted HNF4α protein, and downregulated the expression of a group of genes critical for their functions. Thus, the identity of hepatocytes deficient in Nrf2 was transiently but massively impaired in response to liver mass loss. This event was associated with the coupling of protein depletion of hepatic HNF4α, a master regulator of hepatocyte differentiation, and concomitant inactivation of hepatic Akt1 and p70S6K, critical hepatocyte growth signaling molecules. We conclude that Nrf2 participates in maintaining newly regenerated hepatocytes in a fully differentiated state by ensuring proper regulation of HNF4α, Akt1, and p70S6K during liver regeneration.
登录
查看更多内容
影响因子：
64.5
作者：
He G;Dhar D;Nakagawa H;Font-Burgada J;Ogata H;Jiang Y;Shalapour S;Seki E;Yost SE;Jepsen K;Frazer KA;Harismendy O;Hatziapostolou M;Iliopoulos D;Suetsugu A;Hoffman RM;Tateishi R;Koike K;Karin M
通讯作者：
Karin M
影响因子：
5.3
作者：
Hayhurst, GP;Lee, YH;Gonzalez, FJ
通讯作者：
Gonzalez, FJ
影响因子：
1.9
作者：
Greene, AK;Puder, M
通讯作者：
Puder, M
影响因子：
56.9
作者：
Matsuo, T;Yamaguchi, S;Okamura, H
通讯作者：
Okamura, H
影响因子：
10.5
作者：
Jaramillo MC;Zhang DD
通讯作者：
Zhang DD