β 2-Glycoprotein I inhibits endothelial cell migration through the nuclear factor κB signalling pathway and endothelial nitric oxide synthase activation

Wen Chin Chiu, Tzeon Jye Chiou, An Na Chiang

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

β 2-GPI (β 2-glycoprotein I) is a plasma glycoprotein ascribed with an anti-angiogenic function; however, the biological role and molecular basis of its action in cell migration remain unknown. The aim of the present study was to assess the contribution of β 2-GPI to HAEC (human aortic endothelial cell) migration and the details of its underlying mechanism. Using wound healing and Boyden chamber assays, we found that β 2-GPI inhibited endothelial cell migration, which was restored by its neutralizing antibody. NF-κB (nuclear factor κB) inhibitors and lentiviral siRNA (small interfering RNA) silencing of NF-κB significantly attenuated the inhibitory effect of β 2-GPI on cell migration. Moreover, β 2-GPI was found to induce IκBα (inhibitor of NF-κB) phosphorylation and translocation of p65 and p50. We further demonstrated that mRNA and protein levels of eNOS [endothelial NO (nitric oxide) synthase] and NO production were all increased by β 2-GPI and these effects were remarkably inhibited by NF-κB inhibitors and siRNAs of p65 and p50. Furthermore, β 2-GPI-mediated inhibition of cell migration was reversed by eNOS inhibitors and eNOS siRNAs. The findings of the present study provide novel insight into the ability of β 2-GPI to inhibit endothelial cell migration predominantly through the NF-κB/eNOS/NO signalling pathway, which indicates a potential direction for clinical therapy in vascular diseases.

Original languageEnglish
Pages (from-to)125-133
Number of pages9
JournalBiochemical Journal
Volume445
Issue number1
DOIs
Publication statusPublished - Jul 1 2012
Externally publishedYes

Keywords

  • β -glycoprotein I (β -GPI)
  • Endothelial cell migration
  • Endothelial nitric oxide synthase (eNOS)
  • Nitric oxide (NO)
  • Nuclear factor κB (NF-κB)

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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