4.7 Article

GDF-11 promotes human trophoblast cell invasion by increasing ID2-mediated MMP2 expression

Journal

CELL COMMUNICATION AND SIGNALING
Volume 20, Issue 1, Pages -

Publisher

BMC
DOI: 10.1186/s12964-022-00899-z

Keywords

GDF-11; BMP-11; MMP2; Trophoblast cells; Invasion

Categories

Funding

  1. Research Fund for International Young Scientists [32050410302, 32170868]
  2. National Natural Science Foundation of China

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This study discovers a new biological function and underlying molecular mechanisms of GDF-11 in the regulation of human extravillous trophoblast cell invasion.
Background: Growth differentiation factor-11 (GDF-11), also known as bone morphogenetic protein-11, belongs to the transforming growth factor-beta superfamily. GDF-11 was first identified as an important regulator during embryonic development. Increasing evidence has demonstrated that GDF-11 regulates the development of various organs and its aberrant expressions are associated with the risk of cardiovascular diseases and cancers. Extravillous trophoblast (EVT) cells invasion is a critical event for placenta development and needs to be finely regulated. However, to date, the biological function of GDF-11 in the human EVT cells remains unknown. Methods: HTR-8/SVneo, a human EVT cell line, and primary cultures of human EVT cells were used to examine the effect of GDF-11 on matrix metalloproteinase 2 (MMP2) expression. Matrigel-coated transwell invasion assay was used to examine cell invasiveness. A series of in vitro experiments were applied to explore the underlying mechanisms that mediate the effect of GDF-11 on MMP2 expression and cell invasion. Results: Treatment with GDF-11 stimulates MMP2 expression, in the HTR-8/SVneo and primary human EVT cells. Using a pharmacological inhibitor and siRNA-mediated knockdown approaches, our results demonstrated that the stimulatory effect of GDF-11 on MMP2 expression was mediated by the ALK4/5-SMAD2/3 signaling pathways. In addition, the expression of inhibitor of DNA-binding protein 2 (ID2) was upregulated by GDF-11 and that was required for the GDF-11-stimulated MMP2 expression and EVT cell invasion. Conclusions: These findings discover a new biological function and underlying molecular mechanisms of GDF-11 in the regulation of human EVT cell invasion.

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