Effects of fibronectin, VEGF and angiostatin on the expression of MMPs through different signaling pathways in the JEG-3 cells

Am J Reprod Immunol. 2003 Oct;50(4):273-85. doi: 10.1034/j.1600-0897.2003.00073.x.

Abstract

Problem: The objective of this study was to evaluate the possible signal pathway of fibronectin (FN), vascular endothelial growth factor (VEGF) and angiostatin (AS) on the expression of matrix metalloproteinases (MMPs) in JEG-3 cells.

Methods of study: JEG-3 cells were cultured and were examined for the effect of FN, VEGF and AS on the expression of MMPs by immunocytochemistry, gelatin zymography, Western blot analysis and reverse transcription-polymerase chain reaction (RT-PCR).

Results: We found that up-regulation of the expression of MMPs was induced by FN and VEGF through the focal adhesion kinase (FAK)/mitogen-activated protein kinase (MAPK) and Flt-1/p38SAPK/MAPKAPK2 signaling pathways, respectively. Furthermore, AS down-regulated the expression of MMPs through the integrin alphaVbeta3/FAK signaling pathway independent of the integrin-binding motif Arg-Gly-Asp (RGD).

Conclusion: These data indicate that the expression of MMPs is regulated by many independent factors (such as FN, VEGF and AS) through different signaling pathways which influence the behavior of trophoblast cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiostatins / pharmacology*
  • Cell Line
  • Female
  • Fibronectins / pharmacology*
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Matrix Metalloproteinases / genetics*
  • Matrix Metalloproteinases / metabolism*
  • Pregnancy
  • Protein-Tyrosine Kinases / metabolism
  • Recombinant Proteins / pharmacology
  • Signal Transduction / drug effects
  • Trophoblasts / drug effects
  • Trophoblasts / enzymology
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • Fibronectins
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Angiostatins
  • Protein-Tyrosine Kinases
  • Focal Adhesion Kinase 1
  • Focal Adhesion Protein-Tyrosine Kinases
  • PTK2 protein, human
  • Matrix Metalloproteinases