Aims: Preeclampsia is a gestational complication and the top cause of prenatal mortality and morbidity. The etiology of preeclampsia is associated with defective trophoblast differentiation and functions causing abnormal placental development and maternal-fetal exchange defects. CD147 is a key component of several most abundant protein complexes on human trophoblast. This study aims to determine the role of CD147 in placental development and pathogenesis of preeclampsia.
Methods: The roles of CD147 in trophoblast differentiation and functions were studied using the trophoblast stem cells, trophoblast organoid and placenta-targeted nanoparticles gene suppression models. Placental and serum CD147 expression in early pregnant women (11–13+6 weeks of gestation) who subsequently develop preeclampsia in late pregnancy were compared to normotensive controls.
Results: In pregnant mice, placenta-specific suppression of CD147 leads to preeclampsia-like phenotypes, including elevation of systolic blood pressure, proteinuria, increase of serum sFlt-1 level, renal dysfunction, and defective placental development with reduced number of the invasive trophoblast giant cells, which correspond to the extravillous trophoblast in humans. In vitro functional assays showed that CD147 mediates the differentiation and spiral artery remodeling activities of extravillous trophoblast. CD147 exists as a receptor complex on the plasma membrane of human trophoblast and the interaction of CD147/integrin-β1 complex with Wnt/β-catenin signaling mediates the activities of CD147. The CD147 levels in early placenta villi and serum from pregnant women who developed early-onset preeclampsia in late pregnancy were lower than those with normal pregnancy.
Conclusion: Dysregulation of the CD147 complex confers defective placental development. Clinically, the results of this study indicate a possible research direction for the use of CD147 for the early prediction of Preeclampsia.
Acknowledgments: This work was supported by the National Natural Science Foundation of China (81971396) & Health and Medical Research Fund, the Food and Health Bureau, The Government of the HKSAR (09202056).