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PMID:19255252
| Citation |
Yang, Q, Chen, SP, Zhang, XP, Wang, H, Zhu, C and Lin, HY (2009) Smurf2 participates in human trophoblast cell invasion by inhibiting TGF-beta type I receptor. J. Histochem. Cytochem. 57:605-12 |
|---|---|
| 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)-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. |
| Links |
PubMed PMC2690412 Online version:10.1369/jhc.2009.953166 |
| Keywords |
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; Protein-Serine-Threonine Kinases/biosynthesis; Receptors, Transforming Growth Factor beta/antagonists & inhibitors; Receptors, Transforming Growth Factor beta/biosynthesis; Smad2 Protein/biosynthesis; Trophoblasts/cytology; Trophoblasts/physiology; Ubiquitin-Protein Ligases/biosynthesis; Ubiquitin-Protein Ligases/physiology |
| edit table |
Significance
Annotations
| Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
|---|---|---|---|---|---|---|---|---|
| GO:1901165: positive regulation of trophoblast cell migration |
ECO:0000314: |
P |
Over-expression of Smurf2 enhanced the migration and invasion of HTR-8/SVneo Cells, Figure 2. |
complete | ||||
| GO:0030512: negative regulation of transforming growth factor beta receptor signaling pathway |
ECO:0000314: |
P |
TGF-βR1 was significantly down-regulated in Smurf2 over-expressed cells, Figure 3. |
complete | ||||
|
involved_in |
GO:1901165: positive regulation of trophoblast cell migration |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
|
involved_in |
GO:0030512: negative regulation of transforming growth factor beta receptor signaling pathway |
ECO:0000314: direct assay evidence used in manual assertion |
P |
Seeded From UniProt |
complete | |||
See also
References
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