文章：

FAXDC2在巨核细胞生成中的新功能

Novel function of FAXDC2 in megakaryopoiesis

原文发布日期： 2016-09-30

DOI: 10.1038/bcj.2016.87

类型: Original Article

开放获取: 是

英文摘要：

FAXDC2 (fatty acid hydroxylase domain containing 2) is a member of the fatty acid hydroxylase superfamily. Given the important role of fatty acids in megakaryocytes, we have studied the role of this gene in the development of this lineage. Here we show that the expression of FAXDC2 is constantly elevated during megakaryocyte maturation. In contrast, FAXDC2 is significantly downregulated in acute myeloid leukemia and acute megakaryoblastic leukemia. Moreover, FAXDC2 overexpression promotes the differentiation of megakaryocytic cell lines and primary cells, whereas its knockdown disrupts their maturation. Mechanism study shows that FAXDC2 overexpression enhances extracellular signal-regulated kinase (ERK) signaling and increases RUNX1 (Runt-related transcription factor 1) expression. FAXDC2 also restores megakaryocytic differentiation in cells exposed to an ERK inhibitor or those expressing a dominant negative form of RUNX1. Finally, FAXDC2 overexpression leads to an increase in sphingolipid GM3 synthase, suggesting a potential role of FAXDC2 in lipid metabolism that increases ERK signaling and facilitates megakaryocyte differentiation. Together, these results show that FAXDC2 plays a novel role in development of megakaryocytes and its dysregulation may contribute to abnormal hematopoietic cell development in leukemia.

摘要翻译： 

FAXDC2（脂肪酸羟化酶结构域包含蛋白2）是脂肪酸羟化酶超家族的一员。鉴于脂肪酸在巨核细胞中的重要作用，我们研究了该基因在此细胞谱系发育中的功能。本文发现，FAXDC2的表达在巨核细胞成熟过程中持续上调。相反，在急性髓系白血病和急性巨核细胞白血病中，FAXDC2的表达显著下调。此外，过表达FAXDC2可促进巨核细胞系及原代细胞的分化，而敲低该基因则会破坏其成熟进程。机制研究表明，FAXDC2过表达能增强细胞外信号调节激酶（ERK）信号通路并提升RUNX1（Runt相关转录因子1）的表达水平。即使细胞暴露于ERK抑制剂或表达显性负性RUNX1突变体，FAXDC2仍能恢复其巨核细胞分化能力。最后，FAXDC2过表达会导致鞘脂GM3合酶增加，提示FAXDC2可能通过调节脂代谢增强ERK信号通路，进而促进巨核细胞分化。综上，这些结果表明FAXDC2在巨核细胞发育中发挥着重要作用，其表达失调可能导致白血病中造血细胞的异常发育。

原文链接：

Novel function of FAXDC2 in megakaryopoiesis