Translationally controlled tumor protein promotes liver regeneration by activating mTORC2/AKT signaling
Translationally controlled tumor protein promotes liver regeneration by activating mTORC2/AKT signaling
复制标题
翻译控制的肿瘤蛋白通过激活 mTORC2/AKT 信号促进肝再生
DOI：
10.1038/s41419-020-2231-8
复制
发表时间：
2020-01-23
影响因子：
9
通讯作者：
Dou, Kefeng
中科院分区：
文献类型：
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作者：
Lin, Zhibin;Zhang, Xuan;Dou, Kefeng
翻译控制肿瘤蛋白（Translationally controlled tumor protein，TCTP）是一种具有促细胞增殖活性的蛋白质，在肿瘤的生长和发生中有着广泛的研究。然而，TCTP在肝再生（LR）中的具体作用及其潜在机制仍不清楚。为了研究TCTP在LR期间的贡献，产生杂合TCTP小鼠，并将模拟LR模型应用于TCTP敲低（KD）肝细胞系。结果表明，TCTP-KD可使小鼠LR受损，表现为肝细胞增殖延迟、细胞周期标志物mRNA表达中断、脂质代谢退化和免疫应答异常。此外，发现TCTP通过调节mTORC 2激活PI 3 K/AKT信号传导。最后，血清TCTP的增加率与人类肝切除术后丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）的恢复呈正相关。总之，本研究首次揭示了细胞内TCTP在LR中的关键作用。
Translationally controlled tumor protein (TCTP), which is a protein characterized by its potent proliferation promoting activity, has been well studied in the area of growth and tumorigenesis. However, the specific role of TCTP in liver regeneration (LR) and its underlying mechanism remains unclear. In order to investigate the contribution of TCTP during LR, heterozygous TCTP mice were generated, and a mimic LR model was applied to TCTP-knockdown (KD) hepatic cell lines. The results revealed that TCTP-KD impaired LR in mice, and manifested as the following aspects: delayed proliferation of hepatocytes, accompanied by disruption of the mRNA expression of markers of the cell cycle, degenerated lipid metabolism, and abnormal immune response. Furthermore, it was found out that TCTP activated PI3K/AKT signaling by regulating mTORC2. Lastly, the increasing rate of serum TCTP positively correlated to the recovery of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) after liver resection in humans. In summary, the present study is the first to reveal the crucial role of intracellular TCTP in LR.