Centro Cardiovascular da Universidade de Lisboa, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa, Portugal. Av. Prof. Egas Moniz, 1649-028, Lisbon, Portugal.
Sci Rep. 2020 Feb 21;10(1):3137. doi: 10.1038/s41598-020-60129-9.
Low doses of ionizing radiation (LDIR) activate endothelial cells inducing angiogenesis. In zebrafish, LDIR induce vessel formation in the sub-intestinal vessels during post-embryonic development and enhance the inter-ray vessel density in adult fin regeneration. Since angiogenesis is a crucial process involved in both post-embryonic development and regeneration, herein we aimed to understand whether LDIR accelerate these physiological conditions. Our data show that LDIR upregulate the gene expression of several pro-angiogenic molecules, such as flt1, kdr, angpt2a, tgfb2, fgf2 and cyr61in sorted endothelial cells from zebrafish larvae and this effect was abrogated by using a vascular endothelial growth factor receptor (VEGFR)-2 tyrosine kinase inhibitor. Irradiated zebrafish present normal indicators of developmental progress but, importantly LDIR accelerate post-embryonic development in a VEGFR-2 dependent signaling. Furthermore, our data show that LDIR do not accelerate regeneration after caudal fin amputation and the gene expression of the early stages markers of regeneration are not modulated by LDIR. Even though regeneration is considered as a recapitulation of embryonic development and LDIR induce angiogenesis in both conditions, our findings show that LDIR accelerate post-embryonic development but not regeneration. This highlights the importance of the physiological context for a specific phenotype promoted by LDIR.
低剂量电离辐射（LDIR）激活内皮细胞诱导血管生成。在斑马鱼中，LDIR 在胚胎后发育过程中诱导肠下血管形成，并在成年鳍再生中增强射线间血管密度。由于血管生成是胚胎后发育和再生中涉及的关键过程，因此我们旨在了解 LDIR 是否会加速这些生理状况。我们的数据表明，LDIR 上调了几种促血管生成分子的基因表达，如 flt1、kdr、angpt2a、tgfb2、fgf2 和 cyr61 在斑马鱼幼虫分离的内皮细胞中，并且这种作用被血管内皮生长因子受体（VEGFR）-2 酪氨酸激酶抑制剂所阻断。辐照的斑马鱼具有正常的发育进展指标，但重要的是，LDIR 在 VEGFR-2 依赖性信号转导中加速了胚胎后发育。此外，我们的数据表明，LDIR 不会加速尾鳍切除后的再生，并且 LDIR 不会调节再生早期阶段标志物的基因表达。尽管再生被认为是胚胎发育的重演，并且 LDIR 在这两种情况下都诱导血管生成，但我们的发现表明，LDIR 加速了胚胎后发育，但没有加速再生。这突显了 LDIR 促进特定表型的生理背景的重要性。
