The Transcription Factor Bach1 Suppresses the Developmental Angiogenesis of Zebrafish.
The Transcription Factor Bach1 Suppresses the Developmental Angiogenesis of Zebrafish.
复制标题
转录因子 Bach1 抑制斑马鱼的发育性血管生成
DOI：
10.1155/2017/2143875
复制
发表时间：
2017
影响因子：
--
通讯作者：
Meng D
中科院分区：
文献类型：
--
作者：
Jiang L;Yin M;Xu J;Jia M;Sun S;Wang X;Zhang J;Meng D
Bach 1干扰Wnt/β-catenin信号传导，降低内皮细胞（EC）的增殖、迁移和管形成活性，并抑制手术诱导的后肢缺血（HLI）小鼠的血管生成。然而，Bach 1在斑马鱼发育血管生成过程中的功能仍不清楚。在这里，我们发现斑马鱼Bach 1在斑马鱼早期胚胎发育过程中普遍表达。注射Bach 1b mRNA的Tg（fli 1：gfp）鱼破坏了节间血管（ISV）和背侧纵向吻合血管（DLAV），抑制了内源性Wnt/β-连环蛋白信号传导，Wnt 8a刺激了血管内皮生长因子（VEGF）和白细胞介素-8（IL-8）基因表达在早期胚胎阶段的斑马鱼。此外，染色质免疫沉淀实验证实，Bach 1占据的TCF/LEF结合位点的VEGF启动子在人脐静脉内皮细胞（HUVECs）。Bach 1通过将组蛋白脱乙酰酶1（HDAC 1）募集到HUVECs中的VEGF启动子来抑制VEGF转录。VEGF或IL-8的外源性给药部分挽救了HUVEC中Bach 1驱动的抗血管生成功能。总之，这些观察结果表明Bach 1抑制斑马鱼的发育血管生成，并且该功能与Wnt/β-连环蛋白信号传导以及VEGF和IL-8表达的下降相关。
Bach1 disrupts Wnt/β-catenin signaling, reduces the proliferation, migration, and tube formation activity of endothelial cells (ECs), and suppresses angiogenesis in mice with surgically induced hind-limb ischemia (HLI). However, the function of Bach1 during developmental angiogenesis in zebrafish remains unclear. Here, we found that zebrafish Bach1 was expressed ubiquitously during early embryonic development in zebrafish. Bach1b mRNA injection of Tg(fli1:gfp) fish disrupted intersegmental vessels (ISV) and dorsal longitudinal anastomotic vessels (DLAV) and suppressed endogenous Wnt/β-catenin signaling and Wnt8a stimulated vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8) gene expression at early embryonic stages of zebrafish. Furthermore, chromatin immunoprecipitation experiments confirmed that Bach1 occupied the TCF/LEF-binding site of the VEGF promoter in human umbilical vein endothelial cells (HUVECs). Bach1 inhibited VEGF transcription by recruiting histone deacetylase 1 (HDAC1) to the VEGF promoter in HUVECs. Exogenous administration of VEGF or IL-8 partially rescued Bach1-driven antiangiogenic functions in HUVECs. Taken together, these observations indicate that Bach1 suppresses the developmental angiogenesis of zebrafish and that this function is associated with declines in Wnt/β-catenin signaling and VEGF and IL-8 expression.