Soluble CD146 is increased in pre-eclampsia and interacts with galectin-1 to regulate trophoblast migration through VEGFR-2 receptor.

Abstract Objective To explore the regulatory role of soluble CD146 (sCD146) and its interaction with galectin-1(Gal1) in placenta-mediated complications. Design Prospective pilot and experimental studies. Setting University-affiliated hospital and Academic research laboratory. Patient(s) 115 women included in three groups: 30 healthy non-pregnant women, 50 women with normal pregnancies, and 35 with placenta-mediated pregnancy complications (clinicaltrials.gov identifier: NCT 01736826). Intervention(s) Wound healing experiments were conducted to study trophoblast migration. Main outcome measures(s) Quantification of soluble sCD146 and Gal1 by ELISA. Analysis on trophoblast migration by wound closure. Results Concomitant detection of sCD146 and Gal1 showed lower sCD146 and higher Gal1 concentrations in women with normal pregnancies as compared to non-pregnant women. In addition, follow-up of these women revealed a decrease in sCD146 associated with an increase in Gal1 throughout pregnancy. By contrast, in women with preeclampsia, we found significant higher sCD146 as compared to women with normal pregnancies and no modification of Gal1. We also emphasize a reverse effect of sCD146 and Gal1 since, unlike Gal1, sCD146 inhibits trophoblast migration. Moreover, the migratory effect of Gal1 was abrogated upon the use of an anti-CD146 blocking antibody or the use of interfering RNA to silence VEGFR2 expression. This suggests that trophoblast migration is mediated though the interaction of Gal1 with CD146 further activating the VEGFR2 signaling pathway. Significantly, sCD146 blocked the migratory effects of Gal1 on trophoblasts and hampered its secretion, suggesting that sCD146 acts as a ligand trap. Conclusion Soluble CD146 could be proposed as a biomarker in pre-eclampsia and a potential therapeutic target.