Document Detail

Heparin/heparan sulfate/CD44-v3 enhances cell migration in term placenta-derived immortalized human trophoblast cells.
MedLine Citation:
PMID:  22321833     Owner:  NLM     Status:  MEDLINE    
The function of CD44-v3 and heparin/heparan sulfate (HS) signaling was investigated during trophoblast cell migration to identify their role in the renewal of syncytial layer damage caused by increased hemodynamic turbulence in the intervillous space and maintenance of syncytial integrity in pre-eclampsia. We evaluated the effect of heparin/HS/CD44-v3-mediated processes during scratch wound closure in monolayer immortalized human trophoblast cells derived from term placenta (TCL-1 cells). Western blot analysis showed that these cultured human trophoblast cells express the epidermal growth factor receptor and CD44-v3 but do not express syndecan 4. An in vitro scratch wound healing assay showed enhanced migration of trophoblast cells in a dose-dependent manner in the presence of heparin compared with controls when cultured under serum-free conditions. Conversely, an anti-CD44 function-blocking antibody and CD44 siRNA suppressed the migration of trophoblast cells in the presence of heparin in a similar scratch assay. Furthermore, both heparin treatment and in vitro scratch wounding induced the phosphorylation of p21-activated kinase 1 (PAK1), whereas the anti-CD44-v3 antibody suppressed the heparin-induced phosphorylation of PAK1 in trophoblast cells. These results indicate that heparin/HS/CD44-v3-mediated signaling, in the absence of growth factor networks, enhances the direct repair of the damaged trophoblast layer through the migration of trophoblast cells. This renewed cell coverage may lead to the maintenance of syncytiotrophoblast cell function and an associated reduction in pathogenic soluble factors derived from the damaged trophoblast cells.
Naoko Suga; Motoi Sugimura; Taro Koshiishi; Takashi Yorifuji; Shintaro Makino; Satoru Takeda
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-03
Journal Detail:
Title:  Biology of reproduction     Volume:  86     ISSN:  1529-7268     ISO Abbreviation:  Biol. Reprod.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-05-04     Completed Date:  2012-09-17     Revised Date:  2012-12-06    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  United States    
Other Details:
Languages:  eng     Pagination:  134, 1-8     Citation Subset:  IM    
Department of Obstetrics and Gynecology, School of Medicine, Juntendo University, Tokyo, Japan.
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MeSH Terms
Antibodies, Blocking / metabolism
Anticoagulants / pharmacology*
Antigens, CD44 / biosynthesis*,  genetics,  immunology
Cell Movement / drug effects*
Cells, Cultured
Heparin / pharmacology*
Heparitin Sulfate / pharmacology*
RNA, Small Interfering / administration & dosage
Receptor, Epidermal Growth Factor / biosynthesis
Signal Transduction / drug effects
Syndecan-4 / biosynthesis
Trophoblasts / drug effects*,  metabolism*
p21-Activated Kinases / metabolism
Reg. No./Substance:
0/Antibodies, Blocking; 0/Anticoagulants; 0/Antigens, CD44; 0/CD44 protein, human; 0/RNA, Small Interfering; 0/SDC4 protein, human; 0/Syndecan-4; 9005-49-6/Heparin; 9050-30-0/Heparitin Sulfate; EC protein, human; EC, Epidermal Growth Factor; EC protein, human; EC Kinases

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