PUBLICATION

N-methyl-N-nitrosourea induces zebrafish anomalous angiogenesis through Wnt/β-catenin pathway

Authors
Fu, S., Tan, R., Feng, Y., Yu, P., Mo, Y., Xiao, W., Wang, S., Zhang, J.
ID
ZDB-PUB-220528-15
Date
2022
Source
Ecotoxicology and environmental safety   239: 113674 (Journal)
Registered Authors
Zhang, Jingjing
Keywords
Angiogenesis, MNU, Rspo1, Wnt/β-catenin, Zebrafish
MeSH Terms
  • Animals
  • beta Catenin/genetics
  • beta Catenin/metabolism
  • Neovascularization, Pathologic*/chemically induced
  • Mice
  • Wnt Signaling Pathway*
  • Endothelial Cells/metabolism
  • Zebrafish*/metabolism
  • Methylnitrosourea*/toxicity
(all 9)
PubMed
35623148 Full text @ Ecotoxicol. Environ. Saf.
Abstract
N-methyl-N-nitrosourea (MNU) is a prevalent environmental carcinogen, which leads to tumors in various organs in animal models, while the mechanisms involved were still not fully understood. It is well known that anomalous angiogenesis is a key step in tumorigenesis and progression. In this study, we found that MNU induced abnormal angiogenesis which was accompanied by upregulation of rspo1, p53 and vegfaa in zebrafish embryos. Moreover, it revealed that MNU-induced ectopic sprouting of blood vessels was significantly reduced in rspo1-knockdown but not p53-knockdown embryos, indicating that rspo1 was necessary for MNU-induced abnormal angiogenesis. Additionally, pharmaceutical activation or inhibition of Wnt/β-catenin signaling pathway using (2'Z,3'E)- 6-bromoindirubin-3'-oxime or CCT036477 significantly increased or inhibited the pro-angiogenic effect of MNU on developing zebrafish embryos, which was confirmed by the effect of proliferation and migration in MNU-treated bEnd.3 cells. These data together indicated that rspo1/Wnt/β-catenin/vegfaa axis is involved in the modulation of MNU-induced anomalous angiogenesis.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Fish Conditions Stage Phenotype Figure
s843Tg/s843Tgchemical treatment by environment: N-methyl-N-nitrosoureaPrim-5
s843Tg/s843Tgchemical treatment by environment: N-methyl-N-nitrosoureaPrim-5
s843Tg/s843Tgchemical treatment by environment: N-methyl-N-nitrosoureaPrim-5
s843Tg/s843Tgchemical treatment by environment: N-methyl-N-nitrosoureaPrim-25
s843Tg/s843Tgchemical treatment by environment: N-methyl-N-nitrosoureaPrim-25
s843Tg/s843Tgchemical treatment by environment: N-methyl-N-nitrosoureaPrim-25
s843Tg/s843Tgchemical treatment by environment: N-methyl-N-nitrosoureaLong-pec
s843Tg/s843Tgchemical treatment by environment: N-methyl-N-nitrosoureaLong-pec
s843Tg/s843Tgchemical treatment by environment: N-methyl-N-nitrosoureaLong-pec
s843Tg/s843Tgchemical treatment by environment: N-methyl-N-nitrosoureaLong-pec
1 - 10 of 43
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Mutations / Transgenics
Allele Construct Type Affected Genomic Region
s843TgTransgenic Insertion
    1 - 1 of 1
    Show
    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    Target Reagent Reagent Type
    rspo1MO3-rspo1MRPHLNO
    tp53MO4-tp53MRPHLNO
    1 - 2 of 2
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    Fish
    Fish
    s843Tg/s843Tg
    s843Tg/s843Tg + MO3-rspo1
    s843Tg/s843Tg + MO4-tp53
    1 - 3 of 3
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    Antibodies
    No data available
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    EGFPEFGEGFP
    1 - 1 of 1
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    Mapping
    No data available
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    Citation
    Fu, S., Tan, R., Feng, Y., Yu, P., Mo, Y., Xiao, W., Wang, S., Zhang, J. (2022) N-methyl-N-nitrosourea induces zebrafish anomalous angiogenesis through Wnt/β-catenin pathway. Ecotoxicology and environmental safety. 239:113674.