CD97 Is Decreased in Preeclamptic Placentas and Promotes Human Trophoblast Invasion Through PI3K/Akt/mTOR Signaling Pathway

• Published in: Reproductive sciences (Thousand Oaks, Calif.) Calif.), 2020-08, Vol.27 (8), p.1553-1561
• Main Authors: Shen, Huaxiang, Jin, Minfei, Gu, Shengyi, Wu, Yuelin, Yang, Mengnan, Hua, Xiaolin
• Format: Article
• Language: English
• Subjects: Antigens, CD - metabolism; Cell Movement; Embryology; Female; Gene Knockdown Techniques - methods; Humans; Medicine; Medicine & Public Health; Obstetrics/Perinatology/Midwifery; Original Article; Phosphatidylinositol 3-Kinases - metabolism; Placenta - metabolism; Placenta - pathology; Pre-Eclampsia - metabolism; Pre-Eclampsia - pathology; Pregnancy; Proto-Oncogene Proteins c-akt - metabolism; Receptors, G-Protein-Coupled - metabolism; Reproductive Medicine; Signal Transduction - physiology; TOR Serine-Threonine Kinases - metabolism; Trophoblasts - metabolism; Trophoblasts - pathology
• ISSN: 1933-7191; 1933-7205
• DOI: 10.1007/s43032-020-00183-w

Preeclampsia (PE) is a pregnancy disorder leading to the morbidity and mortality. Despite the development of the understanding of etiology, the only effective treatment of PE is the delivery of the placenta. An improved mastery on the regulation of trophoblast invasion could be meaningful to alleviate the disease burden of PE. Relative expression of CD97 in PE and normal placental tissues was evaluated by quantitative real-time polymerase chain reaction, immunohistology, and Western blot. The CD97 siRNA and expression vector was transfected to cultured human trophoblast HTR-8/SVneo, and the cell invasion as well as the protein expression in PI3K/Akt/mTOR signaling pathway were evaluated. Expression of CD97 is significantly downregulated in PE placental tissues compared to normal controls. The Si-CD97 inhibits HTR-8/SVneo trophoblast cells invasion, as well as the activation of PI3K/Akt/mTOR signaling pathway. In accordance, overexpression of CD97 promotes trophoblast cell invasion. In addition, CD97 regulates FOXC2 expression and showed similar effects on PI3K/Akt/mTOR signaling pathway as specific FOXC2 inhibitor. In short, this study demonstrated the downregulation of CD97 expression in preeclamptic placentas. Further mechanism investigation revealed that CD97 promoted trophoblast invasion by targeting FOXC2 via PI3K/Akt/mTOR signaling pathway, laying the foundation for the development of PE intervention strategy by targeting CD97 in placentation and pathogenesis of PE.