FoxA2通过减少PI3K / Akt / HK2介导的糖酵解来抑制肝祖细胞的增殖。,Journal of Cellular Physiology

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FoxA2通过减少PI3K / Akt / HK2介导的糖酵解来抑制肝祖细胞的增殖。
Journal of Cellular Physiology ( IF 4.5 ) Pub Date : 2020-06-04 , DOI: 10.1002/jcp.29759
Ping Wang _{1,

2} , Min Cong _{1,

2} , Tianhui Liu _{1,

2} , Yaqiong Li ₃ , Lin Liu _{1,

2} , Shujie Sun _{1,

2} , Liying Sun _{4,

5} , Zhijun Zhu _{4,

5} , Hong Ma _{1,

2} , Hong You _{1,

2} , Haiyan Zhang ₃ , Jidong Jia _{1,

2}

Affiliation

FoxA2是肝脏器官发生和体内稳态的重要转录因子。尽管FoxA2的表达降低与慢性肝病有关，但在这些情况下被激活的肝祖细胞（HPC）表达FoxA2。但是，FoxA2在HPC中的功能作用和潜在机制仍然未知。正如免疫染色所揭示的那样，HPC在人肝硬化肝脏和补充有乙硫氨酸（CDE）大鼠的胆碱缺乏饮食的肝脏中表达FoxA2。在从CDE大鼠中分离的HPC中敲除FoxA2可以显着增加细胞增殖和有氧糖酵解。此外，己糖激酶2（HK2）的基因转录，蛋白质表达和酶活性均被上调，并且通过2-脱氧葡萄糖阻断HK2活性显着降低了细胞增殖和有氧糖酵解。《京都议定书》的基因和基因组百科全书分析显示，FoxA2敲低增强了参与磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）途径的基因的转录，并触发了下游Akt磷酸化。Ly294002阻断PI3K / Akt通路可抑制HK2活性，有氧糖酵解和FoxA2敲低细胞的细胞增殖。因此，FoxA2通过抑制PI3K / Akt / HK2调控的需氧糖酵解在HPC的增殖和抑制中起重要作用。FoxA2敲低细胞的增殖和细胞增殖。因此，FoxA2通过抑制PI3K / Akt / HK2调控的需氧糖酵解在HPC的增殖和抑制中起重要作用。和FoxA2击倒细胞中的细胞增殖。因此，FoxA2通过抑制PI3K / Akt / HK2调控的需氧糖酵解在HPC的增殖和抑制中起重要作用。

"点击查看英文标题和摘要"

FoxA2 inhibits the proliferation of hepatic progenitor cells by reducing PI3K/Akt/HK2-mediated glycolysis.

FoxA2 is an essential transcription factor for liver organogenesis and homeostasis. Although reduced expression of FoxA2 has been associated with chronic liver diseases, hepatic progenitor cells (HPCs) that are activated in these circumstances express FoxA2. However, the functional effects and underlying mechanism of FoxA2 in HPCs are still unknown. As revealed by immunostaining, HPCs expressed FoxA2 in human cirrhotic livers and in the livers of choline‐deficient diet supplemented with ethionine (CDE) rats. Knocking down FoxA2 in HPCs isolated from CDE rats significantly increased cell proliferation and aerobic glycolysis. Moreover, gene transcription, protein expression, and the enzyme activities of hexokinase 2 (HK2) were upregulated, and blocking HK2 activities via 2‐deoxyglucose markedly reduced cell proliferation and aerobic glycolysis. Kyoto Encyclopedia of Genes and Genomes analysis revealed that FoxA2 knockdown enhanced the transcription of genes involved in the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (Akt) pathway and triggered downstream Akt phosphorylation. Blocking the PI3K/Akt pathway by Ly294002 inhibited HK2 activities, aerobic glycolysis, and cell proliferation in FoxA2‐knockdown cells. Therefore, FoxA2 plays an important role in the proliferation and inhibition of HPCs by suppressing PI3K/Akt/HK2‐regulated aerobic glycolysis.

更新日期：2020-06-04

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