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Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia
- Publication Year :
- 2017
- Publisher :
- National Academy of Sciences, 2017.
-
Abstract
- Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas this process is interrupted in PE. However, it is not known how the malformed placenta triggers maternal endothelial crisis and the associated manifestations. Here, we have focused on the association of CD81 with PE. CD81, a member of the tetraspanin superfamily, plays significant roles in cell growth, adhesion, and motility. The function of CD81 in human placentation and its association with pregnancy complications are currently unknown. In the present study, we have demonstrated that CD81 was preferentially expressed in normal first TM placentas and progressively down-regulated with gestation advance. In patients with early-onset severe PE (sPE), CD81 expression was significantly up-regulated in syncytiotrophoblasts (STBs), CTBs and the cells in the villous core. In addition, high levels of CD81 were observed in the maternal sera of patients with sPE. Overexpressing CD81 in CTBs significantly decreased CTB invasion, and culturing primary human umbilical vein endothelial cells (HUVECs) in the presence of a high dose of exogenous CD81 resulted in interrupted angiogenesis and endothelial cell activation in vitro. Importantly, the phenotype of human PE was mimicked in the CD81-induced rat model.
- Subjects :
- 0301 basic medicine
Angiogenesis
viruses
CTBS
Umbilical vein
Rats, Sprague-Dawley
0302 clinical medicine
Pre-Eclampsia
Cell Movement
Pregnancy
reproductive and urinary physiology
Multidisciplinary
Biological Sciences
Immunohistochemistry
Trophoblasts
Up-Regulation
Endothelial stem cell
medicine.anatomical_structure
030220 oncology & carcinogenesis
embryonic structures
Female
Chorionic Villi
Pregnancy Trimester, Third
Primary Cell Culture
Down-Regulation
Neovascularization, Physiologic
chemical and pharmacologic phenomena
Biology
Preeclampsia
Tetraspanin 28
Andrology
03 medical and health sciences
Placenta
medicine
Cell Adhesion
Human Umbilical Vein Endothelial Cells
Animals
Humans
Cytotrophoblast
Uterus
Placentation
biochemical phenomena, metabolism, and nutrition
medicine.disease
biological factors
Rats
Disease Models, Animal
Pregnancy Trimester, First
030104 developmental biology
Immunology
Biomarkers
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....fa949d829652ab6baf6f2a134f7321da