Activation of matrix metalloproteinase-26 by HOXA10 promotes embryo adhesion in vitro

Biochem Biophys Res Commun. 2014 Mar 14;445(3):622-8. doi: 10.1016/j.bbrc.2014.02.057. Epub 2014 Feb 22.

Abstract

Successful embryonic implantation requires an effective maternal-embryonic molecular dialogue. However, the detailed mechanisms of epithelial-embryo adhesion remain poorly understood. Here, we report that matrix metalloproteinase-26 (MMP-26) is a novel downstream target gene of homeobox a 10 (HOXA10) in human endometrial cells. HOXA10 binds directly to a conserved TTAT unit (-442 to -439) located within the 5' regulatory region of the MMP-26 gene and regulates the expression and secretion of MMP-26 in a concentration-dependent manner. Moreover, the adenovirus-mediated overexpression of MMP-26 in Ishikawa cells markedly increased BeWo spheroid adhesion. An antibody blocking assay further demonstrated that the promotion of BeWo spheroid adhesion by HOXA10 and MMP-26 was significantly inhibited by pre-treatment with a specific antibody against MMP-26. These results demonstrate that the HOXA10-mediated expression of MMP-26 promotes embryo adhesion during the process of embryonic implantation.

Keywords: Embryo adhesion; HOXA10; MMP-26.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Line, Tumor
  • Embryo Implantation*
  • Endometrium / cytology*
  • Enzyme Activation
  • Female
  • Gene Expression Regulation
  • HEK293 Cells
  • Homeobox A10 Proteins
  • Homeodomain Proteins / metabolism*
  • Humans
  • Matrix Metalloproteinases, Secreted / genetics*
  • Matrix Metalloproteinases, Secreted / metabolism
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Protein Binding

Substances

  • Homeobox A10 Proteins
  • Homeodomain Proteins
  • HOXA10 protein, human
  • MMP26 protein, human
  • Matrix Metalloproteinases, Secreted