期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 288, 期 46, 页码 33181-33192出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.488866
关键词
Cadherins; Invasion; SMAD Transcription Factor; Transforming Growth Factor- (TGF); Trophoblast; Snail; VE-cadherin
资金
- Canadian Institutes of Health Research
Background: Transforming growth factor (TGF)-1 treatment decreases human trophoblast invasion. Results: Smad-dependent up-regulation of Snail mediates TGF-1-induced down-regulation of VE-cadherin. Conclusion: TGF-1 decreases human trophoblast invasion by down-regulating VE-cadherin. Significance: Our results provide important insights into the molecular mechanisms mediating TGF-1-induced down-regulation of VE-cadherin and decreased cell invasion in human trophoblast cells. Human trophoblast cells express transforming growth factor- (TGF-) and TGF- receptors. It has been shown that TGF-1 treatment decreases the invasiveness of trophoblast cells. However, the molecular mechanisms underlying TGF-1-decreased trophoblast invasion are still not fully understood. In the current study, we demonstrated that treatment of HTR-8/SVneo human trophoblast cells with TGF-1 decreased cell invasion and down-regulated the expression of vascular endothelial cadherin (VE-cadherin). In addition, the inhibitory effect of TGF-1 on VE-cadherin was confirmed in primary cultures of human trophoblast cells. Moreover, knockdown of VE-cadherin using siRNA decreased the invasiveness of HTR-8/SVneo cells and primary cultures of trophoblast cells. Treatment with TGF-1 induced the activation of Smad-dependent signaling pathways and the expression of Snail and Slug. Knockdown of Smads attenuated TGF-1-induced up-regulation of Snail and Slug and down-regulation of VE-cadherin. Interestingly, depletion of Snail, but not Slug, attenuated TGF-1-induced down-regulation of VE-cadherin. Furthermore, overexpression of Snail suppressed VE-cadherin expression. Chromatin immunoprecipitation analyses showed the direct binding of Snail to the VE-cadherin promoter. These results provide evidence that Snail mediates TGF-1-induced down-regulation of VE-cadherin, which subsequently contributed to TGF-1-decreased trophoblast cell invasion.
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