Thrombin enhances soluble fms-like tyrosine kinase-1 expression in trophoblasts Possible involvement in the pathogenesis of preeclampsia

Thrombin enhances the secretion of sFlt-1 from trophoblasts, indicating that increased thrombin in the uteroplacental interface may contribute to the pathogenesis of preeclampsia.

Like Comment


Yin Zhao, M.D., Ph.D., Kaori Koga, M.D., Ph.D., Yutaka Osuga , M.D., Ph.D., Miwako Nagai, M.D.; Gentaro Izumi, M.D., Masashi Takamura, M.D., Miyuki Harada, M.D., Ph.D., Yasushi Hirota, M.D., Ph.D., Osamu Yoshino, M.D., Ph.D., Yuji Taketani, M.D., Ph.D.

Vol 98, Issue 4, Pages 917-921



To investigate the possible impact of thrombin on soluble fms-like tyrosine kinase-1 (sFlt-1) expression in trophoblasts




University hospital laboratory.


A trophoblast cell line (HRT-8/SVneo) was treated with thrombin, protease-activated receptor-1 (PAR-1)-specific agonist SFLLERN, and thrombin antagonist PPACK.

Main Outcome Measure(s):

mRNA expression of slft-1, Vascular Endothelial Growth Factor (VEGF) and Placental Growth Factor (PlGF) in trophoblasts, using real-time PCR. The secretion of sFlt-1, VEGF and PlGF protein from trophoblasts, using Enzyme-Linked Immuno Sorbent Assay (ELISA).


Administration of thrombin (10U/ml) and PAR-1 specific agonist SFLLRN (300 M) increased sFlt-1 mRNA expression (4.24 ± 0.74 and 4.21 ± 0.79 fold, respectively, P < 0.05) and protein secretion (5.08 ± 0.42 fold, P < 0.001 and 1.89 ± 0.16 fold, P < 0.05, respectively) in HRT-8/SVneo. The induction of sFlt-1 protein secretion by thrombin was dose dependent. The effect of thrombin was completely reduced by thrombin inhibitor PPACK. Thrombin increased mRNA expression of VEGF (P < 0.05) but did not change VEGF secretion and PlGF mRNA expression and secretion. Conclusion(s):

During placental development, thrombin, generated in the local hemorrhage of the utero-placenta increases trophoblast expression of sFlt-1. Consequently, thrombin may contribute to the pathogenesis of preeclampsia.

Read the full text at:

Fertility and Sterility

Editorial Office, American Society for Reproductive Medicine

Fertility and Sterility® is an international journal for obstetricians, gynecologists, reproductive endocrinologists, urologists, basic scientists and others who treat and investigate problems of infertility and human reproductive disorders. The journal publishes juried original scientific articles in clinical and laboratory research relevant to reproductive endocrinology, urology, andrology, physiology, immunology, genetics, contraception, and menopause. Fertility and Sterility® encourages and supports meaningful basic and clinical research, and facilitates and promotes excellence in professional education, in the field of reproductive medicine.