ArticleCell communication and signaling : CCS2023
Snail mediates GDF-8-stimulated human extravillous trophoblast cell invasion by upregulating MMP2 expression.
Article in Cell communication and signaling : CCS, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 23 citations in OpenAlex.
- Embryonic Mediators of Embryo-Uterus Communication, Implantation and Pregnancy.Molecular reproduction and development · 2026Review
- Targeting the GSK-3β/mTOR axis: a novel pharmacological strategy for preeclampsia prevention and treatment.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- Cross-species insights into placental evolution and diseases at the single-cell resolution.Nature communications · 2026Article
- Metformin suppressed epithelial-mesenchymal transition, cisplatin resistance and metastatic potential of ovarian cancer via inhibiting TGF-β1/Smads.Translational cancer research · 2026Article
- Article
- Growth differentiation factor 7 alleviates the proliferation and metastasis of hepatocellular carcinoma.Liver research (Beijing, China) · 2024Article
- TGFβ signalling: a nexus between inflammation, placental health and preeclampsia throughout pregnancy.Human reproduction update · 2024Review
- GDF-8 improvesFrontiers in cell and developmental biology · 2024Article
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8 authors at 2 institutions in 1 country.
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Abstract
backgroundExtravillous trophoblast (EVT) cell invasion is a tightly regulated process that requires for a normal pregnancy. The epithelial-mesenchymal transition (EMT) has been implicated in EVT cell invasion. Growth differentiation factor-8 (GDF-8), a member of the transforming growth factor-beta (TGF-β) superfamily, is expressed in the human placenta and promotes EVT cell invasion by upregulating the expression of matrix metalloproteinase 2 (MMP2). However, the underlying molecular mechanism of GDF-8-induced MMP2 expression remains undetermined. Therefore, the present study aims to examine the role of Snail and Slug, the EMT-related transcriptional regulators, in GDF-8-stimulated MMP2 expression and cell invasion in HTR-8/SVneo human EVT cell line and primary cultures of human EVT cells.
methodsHTR-8/SVneo and primary cultures of human EVT cells were used to examine the effect of GDF-8 on MMP2 expression and explore the underlying mechanism. For gene silencing and overexpression, the HTR-8/SVneo cell line was used to make the experiments more technically feasible. The cell invasiveness was measured by Matrigel-coated transwell invasion assay.
resultsGDF-8 stimulated MMP2 expression in both HTR-8/SVneo and primary EVT cells. The stimulatory effect of GDF-8 on MMP2 expression was blocked by the inhibitor of TGF-β type-I receptors, SB431542. Treatment with GDF-8 upregulated Snail and Slug expression in both HTR-8/SVneo and primary EVT cells. The stimulatory effects of GDF-8 on Snail and Slug expression were blocked by pretreatment of SB431542 and siRNA-mediated knockdown of SMAD4. Interestingly, using the siRNA knockdown approach, our results showed that Snail but not Slug was required for the GDF-8-induced MMP2 expression and cell invasion in HTR-8/SVneo cells. The reduction of MMP2 expression in the placentas with preeclampsia (PE) was also observed.
conclusionsThese findings discover the physiological function of GDF-8 in the human placenta and provide important insights into the regulation of MMP2 expression in human EVT cells. Video Abstract.
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