PUBLICATION
Microcystin-leucine arginine blocks vasculogenesis and angiogenesis through impairing cytoskeleton and impeding endothelial cell migration by downregulating integrin-mediated Rho/ROCK signaling pathway
- Authors
- Wang, Q., Chen, G., Zhang, Q., Wang, M., Wang, G., Hu, T.
- ID
- ZDB-PUB-210711-4
- Date
- 2021
- Source
- Environmental science and pollution research international 28(47): 67108-67119 (Journal)
- Registered Authors
- Wang, Guixue, Wang, Qilong
- Keywords
- Angiogenesis, Cell migration, Cytoskeleton, Microcystin-leucine arginine, Responsible Editor: Lotfi Aleya, Vasculogenesis
- MeSH Terms
-
- Animals
- Arginine*
- Cytoskeleton
- Endothelial Cells
- Integrins
- Leucine
- Marine Toxins
- Microcystins*
- Rats
- Signal Transduction
- Zebrafish
- PubMed
- 34244946 Full text @ Environ. Sci. Pollut. Res. Int.
Citation
Wang, Q., Chen, G., Zhang, Q., Wang, M., Wang, G., Hu, T. (2021) Microcystin-leucine arginine blocks vasculogenesis and angiogenesis through impairing cytoskeleton and impeding endothelial cell migration by downregulating integrin-mediated Rho/ROCK signaling pathway. Environmental science and pollution research international. 28(47):67108-67119.
Abstract
The main characteristic of eutrophication is cyanobacteria harmful algae blooms. Microcystin-leucine arginine (MC-LR) is considered to be the most toxic and most commonly secondary metabolite produced by cyanobacteria. It has been reported that MC-LR had potential vascular toxicity. However, the mechanism that MC-LR-induced vascular toxicity is very limited and remains to be clarified. The aim of this study was to evaluate the toxic hazard toward the vasculogenesis and angiogenesis of MC-LR. Its effects on vasculogenesis, sprouting angiogenesis, and endothelial cell tube formation were studied. The study showed that MC-LR exposure blocked vasculogenesis in zebrafish embryos, sprouting angiogenesis from rat aorta, and tube formation of human umbilical vein endothelial cells (HUVECs). In addition, MC-LR exposure also induced the disruption of cytoskeletal structures and markedly inhibited endothelial cell (EC) migration from caudal hematopoietic tissue in zebrafish and HUVEC migration. Western blot analysis showed that MC-LR exposure downregulated the expressions of integrin β1, FAK, Rho, and ROCK. Combined with these results, MC-LR could induce disruption of cytoskeleton via downregulating integrin-mediated FAK/ROCK signaling pathway, leading to the inhibition of EC migration, which finally blocked vasculogenesis and angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping