Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and Technology, Wuhan, China.
Department of Molecular Cardiology, Center for Cardiovascular Genetics, Lerner Research Institute, Cleveland Clinic, OH, USA.
FEBS J. 2018 Nov;285(21):4071-4081. doi: 10.1111/febs.14653. Epub 2018 Sep 20.
The phlda3 gene encodes a small, 127-amino acid protein with only a PH domain, and is involved in tumor suppression, proliferation of islet β-cells, insulin secretion, glucose tolerance, and liver injury. However, the role of phlda3 in vascular development is unknown. Here, we show that phlda3 overexpression decreases the expression levels of hemangioblast markers scl, fli1, and etsrp and intersegmental vessel (ISV) markers flk1 and cdh5, and disrupts ISV development in tg(flk1:GFP) and tg(fli1:GFP) zebrafish. Moreover, phlda3 overexpression inhibits the activation of protein kinase B (AKT) in zebrafish embryos, and the developmental defects of ISVs by phlda3 overexpression were reversed by the expression of a constitutively active form of AKT. These data suggest that phlda3 is a negative regulator of hemangioblast specification and ISV development via AKT signaling.
phlda3 基因编码一种含有 PH 结构域的 127 个氨基酸的小蛋白，参与肿瘤抑制、胰岛 β 细胞增殖、胰岛素分泌、葡萄糖耐量和肝损伤。然而，phlda3 在血管发育中的作用尚不清楚。在这里，我们发现过表达 phlda3 会降低成血管细胞标志物 scl、fli1 和 etsrp 以及节间血管 (ISV) 标志物 flk1 和 cdh5 的表达水平，并破坏 tg(flk1:GFP) 和 tg(fli1:GFP) 斑马鱼中的 ISV 发育。此外，phlda3 过表达抑制斑马鱼胚胎中蛋白激酶 B (AKT) 的激活，而过表达 phlda3 引起的 ISV 发育缺陷可被 AKT 的组成性激活形式逆转。这些数据表明，phlda3 通过 AKT 信号通路负调控成血管细胞的特化和 ISV 的发育。
