SiRNA directed against annexin II receptor inhibits angiogenesis via suppressing MMP2 and MMP9 expression

Cell Physiol Biochem. 2015;35(3):875-84. doi: 10.1159/000369745. Epub 2015 Jan 30.

Abstract

Background/aims: Annexin II receptor (AXIIR) is able to mediate Annexin II signal and induce apoptosis, but its role in angiogenesis remains unclear. This study tries to investigate the role of AXIIR in angiogenesis and the plausible molecular mechanism.

Methods/results: RNA interference technology was used to silence AXIIR, and the subsequent effects in vitro and in vivo were evaluated thereafter. Our data indicated that human umbilical vein endothelial cells (HUVECs) expressed AXIIR and knockdown of AXIIR significantly inhibited HUVECs proliferation, adhesion, migration, and tube formation in vitro and suppressed angiogenesis in vivo. Furthermore, AXIIR siRNA induced cell arrest in the S/G2 phase while had no effect on cell apoptosis. We found that these subsequent effects might be via suppressing the expression of matrix metalloproteinase 2and matrix metalloproteinase 9.

Conclusion: AXIIR participates in angiogenesis, and may be a potential therapeutic target for angiogenesis related diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A2 / metabolism
  • Apoptosis / genetics
  • Cell Proliferation / genetics
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Matrix Metalloproteinase 2 / biosynthesis*
  • Matrix Metalloproteinase 9 / biosynthesis*
  • Neovascularization, Pathologic
  • Neovascularization, Physiologic / genetics*
  • Phosphorylation
  • RNA, Small Interfering
  • Receptors, Peptide / antagonists & inhibitors
  • Receptors, Peptide / genetics*

Substances

  • Annexin A2
  • RNA, Small Interfering
  • Receptors, Peptide
  • annexin II receptor, human
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9