PUBLICATION
PMA inhibits endothelial cell migration through activating the PKC-δ/Syk/NF-κB-mediated up-regulation of Thy-1
- Authors
- Wen, H.C., Huo, Y.N., Chou, C.M., Lee, W.S.
- ID
- ZDB-PUB-181106-7
- Date
- 2018
- Source
- Scientific Reports 8: 16247 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Acetophenones/pharmacology
- Animals
- Animals, Genetically Modified
- Benzopyrans/pharmacology
- Cell Movement/drug effects*
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental/drug effects
- Human Umbilical Vein Endothelial Cells
- Humans
- Models, Animal
- NF-kappa B/antagonists & inhibitors
- NF-kappa B/metabolism
- Neovascularization, Physiologic/drug effects
- Neovascularization, Physiologic/physiology*
- Niacinamide/analogs & derivatives
- Niacinamide/pharmacology
- Nitriles/pharmacology
- Protein Kinase C-delta/antagonists & inhibitors
- Protein Kinase C-delta/metabolism
- Pyrimidines/pharmacology
- RNA, Messenger/metabolism
- Signal Transduction/drug effects*
- Sulfones/pharmacology
- Syk Kinase/antagonists & inhibitors
- Syk Kinase/metabolism
- Tetradecanoylphorbol Acetate/pharmacology*
- Thy-1 Antigens/genetics
- Thy-1 Antigens/metabolism*
- Up-Regulation/drug effects
- Zebrafish
- PubMed
- 30389973 Full text @ Sci. Rep.
Citation
Wen, H.C., Huo, Y.N., Chou, C.M., Lee, W.S. (2018) PMA inhibits endothelial cell migration through activating the PKC-δ/Syk/NF-κB-mediated up-regulation of Thy-1. Scientific Reports. 8:16247.
Abstract
We previously showed that overexpression of Thy-1 inhibited and knock-down of Thy-1 enhanced endothelial cell migration. Here, we used phorbol-12-myristate-13-acetate (PMA) as an inducer for Thy-1 expression to investigate molecular mechanisms underlying Thy-1 up-regulation. Our data showed that increased levels of Thy-1 mRNA and protein in endothelial cells were observed at 14-18 hours and 20-28 hours after PMA treatment, respectively. Treatment with PMA for 32 hours induced Thy-1 up-regulation and inhibited capillary-like tube formation and endothelial cell migration. These effects were abolished by Röttlerin (a PKC-δ inhibitor), but not Gö6976 (a PKC-α/β inhibitor). Moreover, pre-treatment with Bay 61-3606 (a Syk inhibitor) or Bay 11-7082 (a NF-κB inhibitor) abolished the PMA-induced Thy-1 up-regulation and migration inhibition in endothelial cells. Using the zebrafish model, we showed that PMA up-regulated Thy-1 and inhibited angiogenesis through the PKC-δ-mediated pathway. Surprisingly, we found that short-term (8-10 hours) PMA treatment enhanced endothelial cell migration. However, this effect was not observed in PMA-treated Thy-1-overexpressed endothelial cells. Taken together, our results suggest that PMA initially enhanced endothelial cell migration, subsequently activating the PKC-δ/Syk/NF-κB-mediated pathway to up-regulate Thy-1, which in turn inhibited endothelial cell migration. Our results also suggest that Thy-1 might play a role in termination of angiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping