GDF-11 promotes human trophoblast cell invasion by increasing ID2-mediated MMP2 expression.
Cell Commun Signal
; 20(1): 89, 2022 06 15.
Article
in En
| MEDLINE
| ID: mdl-35705978
ABSTRACT
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. Video Abstract.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Trophoblasts
/
Bone Morphogenetic Proteins
/
Matrix Metalloproteinase 2
/
Inhibitor of Differentiation Protein 2
/
Growth Differentiation Factors
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
/
Pregnancy
Language:
En
Journal:
Cell Commun Signal
Year:
2022
Type:
Article
Affiliation country:
China