Slc39a5-mediated zinc homeostasis plays an essential role in venous angiogenesis in zebrafish.
Slc39a5-mediated zinc homeostasis plays an essential role in venous angiogenesis in zebrafish.
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Slc39a5介导的锌稳态在斑马鱼静脉血管生成中发挥重要作用
DOI：
10.1098/rsob.200281
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发表时间：
2020-10
期刊：
影响因子：
5.8
通讯作者：
Wang F
中科院分区：
文献类型：
--
作者：
Xia Z;Bi X;Lian J;Dai W;He X;Zhao L;Min J;Wang F
血管生成是一个由多种信号和环境生态位介导的精确过程。虽然必需微量元素锌及其体内平衡对维持细胞正常功能至关重要，但锌是否在血管生成中起作用目前尚不清楚。以斑马鱼胚胎为模型系统，我们发现锌处理显著增加了slc39a5基因的表达，该基因编码锌转运体slc39a5。此外，使用morpholino或CRISPR/ cas9介导的基因编辑敲除slc39a5的表达会导致心脏缺血和尾静脉丛（CVP）中红细胞的积累，以及在早期发育过程中延迟静脉发芽和减少CVP区域的血管袢。进一步分析显示slc39a5突变体的尾静脉增殖明显减少，细胞迁移延迟。在机制水平上，我们发现slc39a5缺陷胚胎中全身锌水平升高，螯合锌恢复了CVP的发育。此外，我们发现在野生型胚胎中锌超载导致CVP形成受损。综上所述，这些结果表明Slc39a5通过调节锌稳态在静脉血管生成中的内皮发芽和迁移中起关键作用。
Angiogenesis is a precise process mediated by a variety of signals and the environmental niche. Although the essential trace element zinc and its homeostasis are essential for maintaining proper cellular functions, whether zinc plays a role in angiogenesis is currently unknown. Using zebrafish embryos as a model system, we found that zinc treatment significantly increased the expression of the slc39a5 gene, which encodes the zinc transporter Slc39a5. Moreover, knocking down slc39a5 expression using either a morpholino or CRISPR/Cas9-mediated gene editing led to cardiac ischaemia and an accumulation of red blood cells in the caudal vein plexus (CVP), as well as delayed venous sprouting and fewer vascular loops in the CVP region during early development. Further analysis revealed significantly reduced proliferation and delayed cell migration in the caudal vein of slc39a5 morphants. At the mechanistic level, we found increased levels of systemic zinc in slc39a5-deficient embryos, and chelating zinc restored CVP development. In addition, we found that zinc overload in wild-type embryos leads to impaired CVP formation. Taken together, these results indicate that Slc39a5 plays a critical role in endothelial sprouting and migration in venous angiogenesis by regulating zinc homeostasis.
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