title: The Transcription Factor Bach1 Suppresses the Developmental Angiogenesis of Zebrafish.
abstract: 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 ofTg(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.
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200127, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yin
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Mengping
authors.initials: M
authors.lastname: Jia
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Shaoyang
authors.initials: S
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biomedical Engineering, School of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Jianyi
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
authors.forename: Dan
authors.identifier: 0000-0001-8588-0235
authors.initials: D
authors.lastname: Meng
mesh_terms: D000818:Animals; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004625:Embryo, Nonmammalian; D004797:Enzyme-Linked Immunosorbent Assay; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics*; D029961:Zebrafish Proteins / Q000378:metabolism
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; D003598:Cytoskeletal Proteins; D042461:Vascular Endothelial Growth Factor A; D051153:Wnt Proteins; D029961:Zebrafish Proteins; C094521:wnt8a protein, zebrafish