Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.
Am J Reprod Immunol. 2012 Mar;67(3):216-23. doi: 10.1111/j.1600-0897.2011.01080.x. Epub 2011 Oct 24.
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.
血管内皮生长因子 C（VEGFC）或 CYR61 都在胎盘发育中起着重要作用，并且可能与子痫前期有关。母体-胎儿界面中的蜕膜自然杀伤（dNK）细胞是 VEGFC 的主要来源。然而，CYR61 对 dNK 细胞中 VEGFC 分泌的调节作用尚不清楚。
使用抗人 CD56 偶联微珠从妊娠早期的蜕膜组织中分离出蜕膜自然杀伤细胞。使用免疫荧光染色检测整合素αvβ3。在存在 CYR61、抗人αvβ3 整合素抗体（LM609）、PI3K 抑制剂（LY294002）或 MEK 抑制剂（U0126）的情况下培养 dNK 细胞。通过实时 PCR 和 ELISA 分别评估 VEGFC mRNA 和蛋白。
外源性 CYR61 在 dNK 细胞中诱导 VEGFC 的表达，无论是在 mRNA 还是蛋白水平上。整合素αvβ3 在 dNK 细胞表面强烈表达。抗αvβ3 整合素抗体抑制了 CYR61 对 VEGFC 表达的作用。LY294002，但不是 U0126，显著降低了 CYR61 对 dNK 细胞的这种促进作用。
VEGFC 分泌的上调主要取决于 CYR61 与 dNK 细胞表面的整合素αvβ3 的结合。PI3K/AKT 信号通路，而不是 ERK/MAPK 信号通路，参与了这种调节。
