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Regulation of Matrix Metalloproteinases-2 and -9 Gene Expression in Cultured Human Fetal Membrane Cells by Influenza

Noboru Uchide1, Kyoko Obatake, Rie Yamada

  • 1Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokuriku University.

Biological & Pharmaceutical Bulletin
|December 2, 2016
PubMed

Insights

Intrauterine influenza virus infection increases matrix metalloproteinases (MMPs) in fetal membrane cells, potentially weakening membranes and contributing to adverse pregnancy outcomes.

Area of Science:

  • Obstetrics and Gynecology
  • Infectious Diseases
  • Molecular Biology

Background:

  • Adverse pregnancy outcomes are sometimes linked to intrauterine infections.
  • Influenza virus infection during pregnancy is a concern for maternal and fetal health.
  • The mechanisms by which intrauterine infections affect pregnancy are not fully understood.

Purpose of the Study:

  • To investigate the impact of influenza virus infection on the gene expression of matrix metalloproteinases (MMPs) in human fetal membrane cells.
  • To explore the potential role of MMPs in the adverse pregnancy outcomes associated with intrauterine influenza.
  • To understand how influenza A (H1N1) affects MMP activity and expression in amnion epithelial, amnion mesenchymal, and chorion trophoblast cells.

Main Methods:

  • Cultured human fetal membrane cells (amnion epithelial, amnion mesenchymal, chorion trophoblast) were infected with influenza A (H1N1) virus.
  • Gene expression and protein activity of MMPs (MMP-2 and MMP-9) were analyzed using gelatin zymography, Western blotting, and reverse transcriptase-PCR.
  • Levels of MMP activity and protein were measured in cell culture supernatants post-infection.

Main Results:

  • Influenza virus infection significantly increased pro-MMP-9 activity in all three cell types 24-48 hours post-infection.
  • Chorion trophoblast cells showed higher spontaneous pro-MMP-2 activity; virus infection enhanced pro-MMP-2 cleavage to its active form in these cells.
  • Virus infection upregulated MMP-9 mRNA expression in all cell types but did not affect MMP-2 mRNA levels.

Conclusions:

  • Influenza virus infection induces MMP-9 gene expression and enhances MMP-2 activation in human fetal membrane cells.
  • These changes in MMPs can lead to extracellular matrix degradation, potentially weakening fetal membranes.
  • The regulation of MMPs by influenza virus in fetal membrane cells may contribute to the etiology of adverse pregnancy outcomes.

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