Wangensteen Kirk J, Zhang Sophia, Greenbaum Linda E, Kaestner Klaus H
Department of Genetics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; Center for Molecular Studies in Digestive and Liver Diseases, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA; Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
Division of Gastroenterology, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA;
Genes Dev. 2015 May 1;29(9):904-9. doi: 10.1101/gad.258855.115.
The fundamental question of which genes are most important in controlling liver regeneration remains unanswered. We employed a parallel screen to test the impact of 43 selected genes on liver repopulation in the Fah(-/-) mouse model of hereditary tyrosinemia. We discovered that the transcription factor Foxa3 was a strong promoter of liver regeneration, while tumor necrosis factor receptor 1 (TNFR1) was the most significant suppressor of repopulation among all of the genes tested. Our approach enabled the identification of these factors as important regulators of liver repopulation and potential drug targets for the promotion of liver repopulation.
在控制肝脏再生过程中，哪些基因最为重要这一基本问题仍未得到解答。我们采用了一种平行筛选方法，以测试43个选定基因对遗传性酪氨酸血症的Fah(-/-)小鼠模型中肝脏再填充的影响。我们发现转录因子Foxa3是肝脏再生的强力促进因子，而肿瘤坏死因子受体1（TNFR1）是所有测试基因中对再填充最显著的抑制因子。我们的方法能够将这些因子鉴定为肝脏再填充的重要调节因子以及促进肝脏再填充的潜在药物靶点。
