Hyaluronan-CD44 interaction promotes growth of decidual stromal cells in human first-trimester pregnancy

PLoS One. 2013 Sep 19;8(9):e74812. doi: 10.1371/journal.pone.0074812. eCollection 2013.

Abstract

Hyaluronan (HA) and its receptor CD44 are expressed at the maternal-fetal interface, but its role in early pregnancy remains unclear. Here, we found that primary decidual stromal cells (DSCs) continuously secreted HA and expressed its receptor CD44. Pregnancy-associated hormones up-regulated HA synthetase (HAS) 2 transcription and HA release from DSCs. High molecular weight-HA (HMW-HA), but not medium molecular weight (MMW-HA) or low molecular weight (LMW-HA), promoted proliferation and inhibited apoptosis of DSCs in a CD44-dependent manner. The in-cell Western analysis revealed HMW-HA activated PI3K/AKT and mitogen-activated protein kinase (MAPK)/ERK1/2 signaling pathways time-dependently. Blocking these pathways by specific inhibitor LY294002 or U0126 abrogated HMW-HA-regulated DSc proliferation and apoptosis. Finally, we have found that HA content, HA molecular weight, HAS2 mRNA level, and CD44 expression were significantly decreased in DSCs from unexplained miscarriage compared with the normal pregnancy. Collectively, our results indicate that higher level and greater molecular mass of HA at maternal-fetal interface contributes to DSc growth and maintenance of DSCs in human early pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abortion, Spontaneous / genetics
  • Abortion, Spontaneous / metabolism
  • Adult
  • Apoptosis
  • Cell Proliferation / drug effects
  • Decidua / cytology*
  • Decidua / metabolism*
  • Female
  • Gene Expression Regulation / drug effects
  • Glucuronosyltransferase / genetics
  • Glucuronosyltransferase / metabolism
  • Gonadal Steroid Hormones / pharmacology
  • Humans
  • Hyaluronan Receptors / metabolism*
  • Hyaluronan Synthases
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / metabolism*
  • Immunohistochemistry
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Molecular Weight
  • Phosphatidylinositol 3-Kinases / metabolism
  • Pregnancy
  • Pregnancy Trimester, First
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Stromal Cells / drug effects
  • Stromal Cells / metabolism*
  • Transcription, Genetic
  • Young Adult

Substances

  • Gonadal Steroid Hormones
  • Hyaluronan Receptors
  • Hyaluronic Acid
  • Glucuronosyltransferase
  • Hyaluronan Synthases
  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3

Grants and funding

This work was supported by the Key Project of Shanghai Basic Research [12JC1401600 to D-JL]; Shanghai Shenkang Foundation [SHDC12010122 to D-JL]; Shanghai PuJiang Talent Program [10PJ1401600 to M-RD]; and National Nature Science Foundation of China [NSFC30910103909 and NSFC31270969 to D-JL, NSFC81070537 and NSFC31171437 to M-RD]; and the Natural Science Research Program for Colleges and Universities of Jiangsu Province [10KJB320021 to RZ]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.