CYR61 modulates the vascular endothelial growth factor C expression of decidual NK cells via PI3K/AKT pathway

Either vascular endothelial growth factor C (VEGFC) or CYR61 plays an important role in placental development and may be involved in pre-eclampsia. Decidual natural killer (dNK) cells are the main source of VEGFC in the maternal-fetal interface. However, it is unclear about CYR61 on the regulation of VEGFC secretion in dNK cells.

Decidual natural killer cells were isolated from decidual tissues of first trimester of pregnancy with anti-human CD56-conjugated microbeads. Integrin αvβ3 was detected using immunofluorescent staining. dNK cells were cultured in the presence of CYR61, anti-human αvβ3 integrin antibody (LM609), PI3K inhibitor (LY294002), or MEK inhibitor (U0126). VEGFC mRNA and protein were evaluated by real-time PCR and ELISA, respectively.

Exogenous CYR61 induced the expression of VEGFC in dNK cells in both mRNA and protein levels. Integrin αvβ3 was strongly expressed on dNK cell surface. Anti-αvβ3 integrin antibody inhibited the effect of CYR61 on VEGFC expression. LY294002, but not U0126, significantly reduced this promotion effect of CYR61 on dNK cells.

The upregulation of VEGFC secretion mainly depends on CYR61 binding with integrin αvβ3 on the surface of dNK cells. PI3K/AKT, rather than the ERK/MAPK signal, is involved in the regulation.