Document Detail


Smurf2 participates in human trophoblast cell invasion by inhibiting TGF-beta type I receptor.
MedLine Citation:
PMID:  19255252     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Successful embryo implantation depends on the ability of the trophoblast cells to invade the endometrium and the receptivity of the endometrium. Unlike tumor invasion, trophoblast invasion is spatio-temporaly restricted. Transforming growth factor (TGF)-beta is a key inhibitory factor in the invasion of early trophoblast cells. Smad ubiquitination regulatory factor 2 (Smurf2), a HECT type E3 ubiquitin ligase, is an important regulator of the TGF-beta signaling pathway, targeting TGF-beta receptors and various Smads for proteasome-mediated degradation. In this context, we wished to determine whether Smurf2 has a physiological role during embryo implantation, especially in trophoblast invasion. We examined the spatio-temporal expression of Smurf2 in human placental villi and the function of Smurf2 in trophoblast cell migration and invasion in a model system involving a human extravillous trophoblast cell line, HTR-8/SVneo. Results from RT-PCR and immunohistochemical studies showed that expression of Smurf2 in placental villi was the highest during the first trimester and decreased as the pregnancy progressed. Overexpression of Smurf2 in HTR-8/SVneo cells reduced TGF-beta type I receptor levels, and enhanced cell migration and invasion. Conversely, RNA interference-mediated downregulation of Smurf2 resulted in a significant increase in TGF-beta type I receptor protein levels. However, the levels of Smad2, another potential target of Smurf2, remained unchanged. In conclusion, the present study suggests that Smurf2 promotes trophoblast cell migration and invasion, and this function may involve downregulation of TGF-beta type I receptor.
Authors:
Qing Yang; Sheng-Ping Chen; Xiao-Ping Zhang; Hongmei Wang; Cheng Zhu; Hai-Yan Lin
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-02
Journal Detail:
Title:  The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society     Volume:  57     ISSN:  0022-1554     ISO Abbreviation:  J. Histochem. Cytochem.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-18     Completed Date:  2009-06-26     Revised Date:  2010-09-23    
Medline Journal Info:
Nlm Unique ID:  9815334     Medline TA:  J Histochem Cytochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  605-12     Citation Subset:  IM    
Affiliation:
State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
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MeSH Terms
Descriptor/Qualifier:
Cell Line
Cell Movement
Chorionic Villi / metabolism
Down-Regulation
Embryo Implantation
Female
Gene Knockdown Techniques
Humans
Pregnancy
Pregnancy Trimesters
Protein-Serine-Threonine Kinases / antagonists & inhibitors*,  biosynthesis
Receptors, Transforming Growth Factor beta / antagonists & inhibitors*,  biosynthesis
Smad2 Protein / biosynthesis
Trophoblasts / cytology,  physiology*
Ubiquitin-Protein Ligases / biosynthesis,  physiology*
Chemical
Reg. No./Substance:
0/Receptors, Transforming Growth Factor beta; 0/SMAD2 protein, human; 0/Smad2 Protein; EC 2.7.1.11/TGF-beta type I receptor; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 6.3.2.19/SMURF1 protein, human; EC 6.3.2.19/Ubiquitin-Protein Ligases
Comments/Corrections

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