INSERM, UMR1053, Bordeaux, France.
BaRITOn (Bordeaux Research in Translational Oncology), Université de Bordeaux, Bordeaux, France.
Liver Int. 2021 Jun;41(6):1423-1429. doi: 10.1111/liv.14886. Epub 2021 Apr 19.
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 ). Interestingly, hepatocyte proliferation is strongly impaired in Reptin 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 model, we have observed a progressive loss of Reptin invalidation associated with an atypical liver regeneration. Hypertrophic and proliferative hepatocytes gradually replace Reptin 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.
先前的研究表明，Reptin 在肝细胞癌中过表达，并且对体外增殖和细胞存活是必需的。然而，其在体内的病理生理作用尚不清楚。我们旨在使用肝 Reptin 敲除模型（Reptin -/- ）研究 Reptin 在肝再生后肝细胞增殖中的作用。有趣的是，Reptin -/- 小鼠在部分肝切除后 36 小时，肝细胞增殖明显受损，与细胞周期蛋白 A 表达和 mTORC1 和 MAPK 信号通路的减少有关，导致肝再生受损。此外，在 Reptin 模型中，我们观察到与非典型肝再生相关的 Reptin 失活的逐渐丧失。肥大和增殖的肝细胞逐渐取代 Reptin 萎缩的肝细胞。总之，我们的结果表明 Reptin 在体内和肝再生中是肝细胞增殖所必需的，并且在肝细胞存活和肝稳态中发挥关键作用。
