Abstract
In brief: The release of basigin protein by human placental trophoblast cells via extracellular vesicle release is a regulated process. This study shows interactions of trophoblast cells with uterine cells during early placental development. : Successful pregnancy relies on the regulated invasion of trophoblast cells into the maternal endometrium and subsequent remodeling of spiral arteries. Various factors are involved in regulating these processes, including matrix metalloproteinases (MMPs), cytokines such as interleukins (IL) and transforming growth factor β (TGFβ), and hypoxic conditions. Basigin (BSG), a glycosylated protein, plays an important role in MMP induction and inflammation. The role of BSG during early stages of placental development is not yet clear, nor is the process by which BSG is secreted by trophoblast cells. This study investigated the mechanism of BSG secretion from trophoblast cells in extracellular vesicles (EVs), and whether BSG release in EVs is a regulated process. RT-PCR was used to identify BSG isoforms 2, 3, and 4 in the trophoblast-like cell lines JAR, JEG-3, and HTR-8/SVneo. BSG protein expression was confirmed in trophoblast cell lines and conditioned medium by immunoblotting. We confirmed that BSG is released from HTR-8/SVneo cells via EVs. Treatment of HTR-8/SVneo cells with the protein kinase C activator PMA increased release of BSG-containing EVs, whereas the protein kinase C inhibitor Bis reduced release. Hypoxia/reoxygenation increased BSG protein in released EVs. IL-1β enhanced, while TGF-β1 reduced BSG in released EVs. This effect occurred at the post-transcriptional level, as the quantity of EVs released and levels of BSG mRNA expression in HTR-8/SVneo cells were not altered. Our findings support that BSG, released via EVs, may play an important role in facilitating interactions between trophoblast cells and uterine cells during early stages of placental development.