Research Papers:

Transforming growth factor β1 promotes invasion of human JEG-3 trophoblast cells via TGF-β/Smad3 signaling pathway

Zhongying Huang _, Shangwei Li, Wei Fan and Qianhong Ma

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Oncotarget. 2017; 8:33560-33570. https://doi.org/10.18632/oncotarget.16826

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Zhongying Huang1, Shangwei Li1, Wei Fan1, Qianhong Ma1

1Department of Obsterics and Gynecology, West China 2nd Hospital, University of Sichuan, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Chengdu 610041, People’s Republic of China

Correspondence to:

Zhongying Huang, email: [email protected]

Wei Fan, email: [email protected]

Keywords: TGF-β signaling, Smads, matrix metalloproteinases, trophoblast

Received: September 24, 2016     Accepted: March 26, 2017     Published: April 04, 2017


Transforming growth factor (TGF)-β1 is involved invasion of human trophoblasts. However, the underlying mechanisms remain unclear. In this study, we performed Transwell assay and found that TGF-β1 promoted the invasion of trophoblast cell line JEG-3. Treatment with TGF-β1 up-regulated the expression of receptor-regulated Smad transcription factors Smad2 and Smad3, and two invasive-associated genes, namely, matrix metallopeptidase (MMP)-9 and MMP-2, in JEG-3 cells. Over-expressing activin receptor-like kinase (ALK) 5, the TGF-β type I receptor (TβRI) enhanced the up-regulation of Smad2, Smad3, MMP-9, and MMP-2 induced by TGF-β1, whereas application of TβRI inhibitor SB431542 diminished the stimulatory effects of TGF-β1 on these genes. Furthermore, transfection of Smad3 and ALK-5 seperately or in combination into JEG-3 cells before TGF-β1 treatment significantly increased the expression of MMP-9 and MMP-2. By contrast, silencing Smad3 and Smad2 by siRNAs significantly decreased the expression of MMP-9 and MMP-2, with Smad3 silence having a more potent inhibitory effect. Inhibiting TβRI with SB431542 or knockdown of Smad3, but not Smad2, abolished the stimulatory effect of TGF-β1 on the invasion of JEG-3 cells. Taken together, the results indicate that TGF-β1 activates the Smads signaling pathway in JEG-3 trophoblast cells and Smad3 play a key role in TGF-β1-induced invasion of JEG-3 and up-regulation of MMP-9 and MMP-2 expression.

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