The Role of MGAT5 in Human Umbilical Vein Endothelial Cells

Reprod Sci. 2017 Feb;24(2):313-323. doi: 10.1177/1933719116655602. Epub 2016 Sep 27.

Abstract

Preeclampsia (PE) is associated with shallow invasion of the trophoblast and insufficient remodeling of the uterine spiral artery. Glycosylation reactions are catalyzed by glycosyltransferases including N-acetylglucosaminyltransferase V (MGAT5) and accumulating evidence suggests that MGAT5 is correlated with the migration, proliferation, and survival of various cell types. Our previous study confirmed that MGAT5 is a negative regulator of trophoblast migration and invasion via the direct or indirect inhibition of matrix metalloproteinase 2/9 activity. The primary purpose of this study is to investigate the role of MGAT5 in the function of human umbilical vein endothelial cells (HUVECs) during the development of PE. We observed that MGAT5 was specifically localized within the decidual cells and endothelial cells in maternal decidual tissues. The expression of MGAT5 was elevated in PE placentas compared with the normal control placentas. Moreover, the expression of MGAT5 was increased in hypoxia-reoxygenation (H/R)-treated HUVECs. The knockdown of MGAT5 and PD98059 treatment significantly enhanced cell migration in vitro, promoted tube formation capacity, and inhibited apoptosis in H/R-exposed HUVECs. Our data suggest that oxidative stress induces the overexpression of MGAT5 via the regulation of the focal adhesion kinase-extracellular signal-regulated kinase signaling pathway, which, in turn, affects the function of endothelial cells, which then participates in the pathogenesis of PE.

Keywords: N-acetylglucosaminyltransferase V (MGAT5); human umbilical vein endothelial cells (HUVECs); preeclampsia.

MeSH terms

  • Adult
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Decidua / cytology
  • Decidua / drug effects
  • Decidua / metabolism*
  • Female
  • Flavonoids / pharmacology
  • Gene Knockdown Techniques
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • N-Acetylglucosaminyltransferases / genetics
  • N-Acetylglucosaminyltransferases / metabolism*
  • Oxidative Stress / physiology*
  • Placenta / metabolism
  • Pre-Eclampsia / metabolism*
  • Pregnancy
  • Signal Transduction / physiology

Substances

  • Flavonoids
  • Mgat5 protein, human
  • N-Acetylglucosaminyltransferases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one