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
- Endothelial Cells/metabolism
- Methylnitrosourea*/toxicity
- Mice
- Neovascularization, Pathologic*/chemically induced
- Wnt Signaling Pathway*
- Zebrafish*/metabolism
- beta Catenin/genetics
- beta Catenin/metabolism
- PubMed
- 35623148 Full text @ Ecotoxicol. Environ. Saf.
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.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping