PMA inhibits endothelial cell migration through activating the PKC-δ/Syk/NF-κB-mediated up-regulation of Thy-1

Heng Ching Wen, Yen Nien Huo, Chih Ming Chou, Wen Sen Lee

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2 Citations (Scopus)

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.

Original languageEnglish
Article number16247
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Cell Movement
Acetates
Up-Regulation
Endothelial Cells
phorbol-12-myristate
Zebrafish
Messenger RNA
Proteins

ASJC Scopus subject areas

  • General

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PMA inhibits endothelial cell migration through activating the PKC-δ/Syk/NF-κB-mediated up-regulation of Thy-1. / Wen, Heng Ching; Huo, Yen Nien; Chou, Chih Ming; Lee, Wen Sen.

In: Scientific Reports, Vol. 8, No. 1, 16247, 01.12.2018.

Research output: Contribution to journalArticle

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