Applicants - Role of galectin-14, a placental signalling protein in inflammatory pregnancy syndromes

Seventy percent of pregnancies and 15-20% of clinically recognized pregnancies end in miscarriages. The dysregulation of maternal-fetal immune tolerance and uterine or maternal systemic inflammatory processes may be causal for most of these failed pregnancies. Trophoblastic extracellular vesicles (TEVs) may induce maternal-fetal immune tolerance, and their changed number and biological composition may lead to the failure of immune tolerance, inflammatory diseases and complications of pregnancy. Galectin-14 is a signaling protein uniquely produced by the placenta and expressed by TEVs, which may have a key role in modulating maternal-fetal immune regulation and local or systemic inflammatory processes.

Within the Medinprot Synergy co-operation, the Reproductive Immunology Research Group of the Department of Genetics, Cell and Immunobiology of the Semmelweis University led by Éva Pállinger as well as the Systems Biology of Reproduction Momentum Research Group of the Hungarian Academy of Sciences Research Centre for Natural Sciences led by Nándor Gábor Than characterize the molecular mechanisms of TEV-target cell interactions. In addition, they examine the biological effects of TEV-expressed galectin-14 on the maternal immune system and its role in inflammatory conditions in pregnancy complications. The research focuses on the establishment of galectin-14 overexpressing BeWo cell clones, the examination of the immunobiological effects of TEVs secreted by these BeWo clones, as well as on the study of the potential biomarker role of galectin-14+ TEVs in blood taken from women with spontaneous or induced abortions.

Up to date, the research teams developed and tested in vitro experimental model systems to examine the immunobiological effects of TEVs and galectin-14; validated several laboratory methods (FACS, DLS, ELMI, realtime impedimetry) for the study of BeWo secreted TEVs; performed the comparative analysis of galectin-14 and its protein homologues; characterized anti-galectin-14 antibodies with Western blot, immunohistochemistry and FACS methods; established galectin-14 overexpressing BeWo cell lines; characterized galectin-14 overexpressing TEVs with FACS; collected peripheral blood samples from women with spontaneous or induced abortions as well as healthy pregnant women. Studies under start include the characterization of galectin-14 expression pattern on circulating TEVs, the identification of target cells of galectin-14+ TEVs, and the investigation of the biological activity of galectin-14+ TEVs.

The collaborating groups also successfully developed new synergies with four research groups at Semmelweis University, the Hungarian Academy of Sciences and the University of Basel; won MedInProt AdHoc and University of Basel Innovation Pilot grants with this expanded research platform; assembled OTKA grant application; and preparated for the submission of foreign grant applications with the same collaborative network.