Protein Z Promotes Proliferation in Vascular Endothelial Cell Mediated by Chemokine C-X-C-Motif Receptor 4.

Abstract

Preeclampsia (PE) is a multisystem progressive disease unique to pregnancy, seriously affecting maternal and infant health. Previous studies have shown that PE is associated with changes in vascular endothelial cells, but the specific mechanism is unclear. In this study, we assessed the effects of chemokine C-X-C-motif receptor 4 (CXCR4) on endothelial cells and explored the potential mechanisms. Human placental microvascular endothelial cells (HPVEC) were exposed to protein Z (PZ), qRT-PCR and Western blotting were used to detect the expression of proliferation related genes and proteins, such as PI3K/Akt/ERK. Meanwhile, qRT-PCR and Western blotting were used to detect the expression of anticoagulation markers PGI2 and t-PA. Then, HPVEC were transfected with CXCR4 siRNA or NC siRNA. The expression of proliferation related genes and proteins were also detected. Finally, PZ and CXCR4 were co-cultivated with different fluorescent labels, the binding sites of the two proteins were observed under confocal laser scanning microscopy (CLSM). PZ promoted the proliferation and expression of anticoagulant markers PGI2 and t-PA in HPVEC. CXCR4 silencing could inhibit the proliferation of HPVEC which stimulated by PZ. CLSM showed that the binding site of PZ and CXCR4 was located on the cell membrane. In conclusion, our results suggested that PZ promote the expression of PGI2/t-PA and affect the PI3K/Akt/ERK signaling pathway by binding with CXCR4 which improved our understanding of the molecular mechanisms involved in HPVEC.