In:
Journal of Histochemistry & Cytochemistry, SAGE Publications, Vol. 57, No. 6 ( 2009-06), p. 605-612
Abstract:
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)-β 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-β signaling pathway, targeting TGF-β 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-β type I receptor levels, and enhanced cell migration and invasion. Conversely, RNA interference—mediated downregulation of Smurf2 resulted in a significant increase in TGF-β 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-β type I receptor.
Type of Medium:
Online Resource
ISSN:
0022-1554
,
1551-5044
DOI:
10.1369/jhc.2009.953166
Language:
English
Publisher:
SAGE Publications
Publication Date:
2009
detail.hit.zdb_id:
1421306-0
SSG:
12
