Ye Xiangli, Qian Yu, Wang Qian, Yuan Wuzhou, Mo Xiaoyang, Li Yongqing, Jiang Zhigang, Xu Wei, Deng Yun, Wan Yongqi, Fan Xiongwei, Wu Xiushan, Wang Yuequn
The Center for Heart Development, Key Lab of MOE for Development Biology and Protein Chemistry, College of Life Sciences, Hunan Normal University, Changsha, 410081, Hunan, China.
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China.
PLoS One. 2016 Jan 22;11(1):e0146468. doi: 10.1371/journal.pone.0146468. eCollection 2016.
Previous studies have demonstrated that Smyd1 plays a critical role in cardiomyocyte differentiation, cardiac morphogenesis and myofibril organization. In this study, we uncovered a novel function of Smyd1 in the regulation of endothelial cells (ECs). Our data showed that Smyd1 is expressed in vascular endothelial cells, and knockdown of SMYD1 in endothelial cells impairs EC migration and tube formation. Furthermore, Co-IP and GST pull-down assays demonstrated that SMYD1 is associated with the Serum Response Factor (SRF). EMSA assays further showed that SMYD1 forms a complex with SRF and enhances SRF DNA binding activity. Our studies indicate that SMYD1 serves as an SRF-interacting protein, enhances SRF DNA binding activity, and is required for EC migration and tube formation to regulate angiogenesis.
先前的研究表明，Smyd1在心肌细胞分化、心脏形态发生和肌原纤维组织中起关键作用。在本研究中，我们发现了Smyd1在调节内皮细胞（ECs）方面的新功能。我们的数据显示，Smyd1在血管内皮细胞中表达，在内皮细胞中敲低SMYD1会损害EC迁移和管形成。此外，免疫共沉淀和谷胱甘肽-S-转移酶下拉试验表明，SMYD1与血清反应因子（SRF）相关。电泳迁移率变动分析试验进一步表明，SMYD1与SRF形成复合物并增强SRF的DNA结合活性。我们的研究表明，SMYD1作为一种与SRF相互作用的蛋白，增强SRF的DNA结合活性，是EC迁移和管形成以调节血管生成所必需的。
