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

• Published in: PloS one Vol. 8; no. 9; p. e74812
• Main Authors: Zhu, Rui, Wang, Song-Cun, Sun, Chan, Tao, Yu, Piao, Hai-Lan, Wang, Xiao-Qiu, Du, Mei-Rong, Da-Jin Li
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 19.09.2013; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Abortion; Abortion, Spontaneous - genetics; Abortion, Spontaneous - metabolism; Adult; AKT protein; Apoptosis; CD44 antigen; Cell Proliferation - drug effects; Cytokines; Decidua; Decidua - cytology; Decidua - metabolism; Extracellular matrix; Extracellular signal-regulated kinase; Female; Fetuses; Gene expression; Gene Expression Regulation - drug effects; Glucuronosyltransferase - genetics; Glucuronosyltransferase - metabolism; Gonadal Steroid Hormones - pharmacology; Growth; Growth factors; Gynecology; Hormones; Humans; Hyaluronan Receptors - metabolism; Hyaluronan Synthases; Hyaluronic acid; Hyaluronic Acid - chemistry; Hyaluronic Acid - metabolism; Hydration; Immunohistochemistry; Immunology; Kinases; Laboratories; Ligases; Low molecular weights; MAP kinase; Miscarriage; Mitogen-Activated Protein Kinase 1 - metabolism; Mitogen-Activated Protein Kinase 3 - metabolism; Molecular Weight; Obstetrics; Phosphatidylinositol 3-Kinases - metabolism; Placenta; Pregnancy; Pregnancy Trimester, First; Pregnant women; Protein Binding; Protein kinase; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction; Signaling; Stromal cells; Stromal Cells - drug effects; Stromal Cells - metabolism; Transcription; Transcription, Genetic; Young Adult; United States > US; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0074812

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.