Reptin/RUVBL2 is required for hepatocyte proliferation in vivo, liver regeneration and homeostasis
Reptin/RUVBL2 is required for hepatocyte proliferation in vivo, liver regeneration and homeostasis
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DOI：
10.1111/liv.14886
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发表时间：
2021-04-19
影响因子：
6.7
通讯作者：
Benhamouche-Trouillet, Samira
中科院分区：
文献类型：
--
作者：
Javary, Joaquim;Allain, Nathalie;Benhamouche-Trouillet, Samira
以前的研究表明，Reptin在肝细胞癌中过表达，并且它是体外增殖和细胞存活所必需的。然而，其在体内的病理生理作用仍然未知。我们的目的是使用肝Reptin敲除模型（Reptin（LKO））研究Reptin在再生后肝细胞增殖中的作用。有趣的是，部分肝切除术后36 h，Reptin（LKO）小鼠的肝细胞增殖严重受损，与细胞周期蛋白A表达和mTORC1和MAPK信号转导的减少相关，导致肝再生受损。此外，在Reptin（LKO）模型中，我们观察到与非典型肝再生相关的Reptin失效的进行性损失。肥大和增殖的肝细胞逐渐取代Reptin（KO）的营养不良的肝细胞。总之，我们的结果表明，Reptin是体内肝细胞增殖和肝脏再生所需的，并且它在肝细胞存活和肝脏稳态中发挥着至关重要的作用。
Previous studies have shown that Reptin is overexpressed in hepatocellular carcinoma and that it is necessary for in vitro proliferation and cell survival. However, its pathophysiological role in vivo remains unknown. We aimed to study the role of Reptin in hepatocyte proliferation after regeneration using a liver Reptin knock-out model (Reptin(LKO)). Interestingly, hepatocyte proliferation is strongly impaired in Reptin(LKO) mice 36 h after partial hepatectomy, associated with a decrease of cyclin-A expression and mTORC1 and MAPK signalling, leading to an impaired liver regeneration. Moreover, in the Reptin(LKO) model, we have observed a progressive loss of Reptin invalidation associated with an atypical liver regeneration. Hypertrophic and proliferative hepatocytes gradually replace Reptin(KO) hypotrophic hepatocytes. To conclude, our results show that Reptin is required for hepatocyte proliferation in vivo and liver regeneration and that it plays a crucial role in hepatocyte survival and liver homeostasis.