Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia.
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.
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Li
L
Shen
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Zhenyu
Z
Diao
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Hai-Xiang
HX
Sun
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Gui-Jun
GJ
Yan
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Zhiqun
Z
Wang
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Ruo-Tian
RT
Li
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Yimin
Y
Dai
Department of Pathology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Jingmei
J
Wang
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Jie
J
Li
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Hailing
H
Ding
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Guangfeng
G
Zhao
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Mingming
M
Zheng
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Pingping
P
Xue
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China.
Mo
M
Liu
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA 94143-0665 yalihu@nju.edu.cn Yan.Zhou@ucsf.edu.
Yan
Y
Zhou
Department of Obstetrics and Gynecology, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing 210008, China; yalihu@nju.edu.cn Yan.Zhou@ucsf.edu.
Yali
Y
Hu
D000818:Animals; D015415:Biomarkers / Q000097:blood; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology; D002824:Chorionic Villi / Q000378:metabolism; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007150:Immunohistochemistry; D018919:Neovascularization, Physiologic / Q000502:physiology; D010929:Placentation / Q000502:physiology*; D011225:Pre-Eclampsia / Q000097:blood / Q000473:pathology*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D060225:Tetraspanin 28 / Q000097:blood / Q000378:metabolism*; D014327:Trophoblasts / Q000502:physiology*; D015854:Up-Regulation; D014599:Uterus / Q000098:blood supply
D015415:Biomarkers; C554798:CD81 protein, human; C554797:Cd81 protein, rat; D060225:Tetraspanin 28
CD81; CTB invasion; early-onset preeclampsia; endothelial cell dysfunction; rat model