Trophoblast-derived CD81 decreased eNOS expression in endothelial cell during preeclampsia development
Year: 2025
Type: article
Abstract: Trophoblast shallow invasion and maternal vascular endothelial cell damage are recognized as key pathophysiological changes associated with preeclampsia (PE). Our previous study demonstrated that CD81 inhibits trophoblast cell invasion and induces endothelial cell dysfunction. In present study, we investigated whether trophoblast-derived CD81 influences endothelial cell permeability and the expression of endothelial nitric oxide synthase (eNOS) in endothelial cell, also we explored the related molecular mechanisms. Firstly, we observed that eNOS protein level was decreased in the placenta of patients with severe preeclampsia (sPE) by western blotting (WB) analysis. Immunohistochemical results indicated that eNOS expression was down-regulated in the villous of sPE patients. Secondly, we found that primary human umbilical vein endothelial cells (HUVECs) treated with Ad-CD8-media derived from HTR-8/SV neo cells exhibited increased cell permeability compared to those treated with Ad-CTL-media. Conversely, the cell permeability of siCD81-media treated primary HUVECs was inhibited. The expressions of eNOS, Akt S473 and PDK1 in HUVECs exposed to Ad-CD81-media from trophoblasts were reduced; while treated with siCD81-media, the expressions of these moleculars were elevated in HUVECs. Furthermore, using the inhibitor of PI3K/Akt, we discovered that LY294002 could significantly reverse the effects of CD81-related media on the expressions of eNOS, Akt S473 and PDK1 in the HUVECs. Finally, we found the expressions of Akt S473 and PDK1 were reduced in placenta of sPE patients by WB analysis. In conclusion, the present study indicated that trophoblast-derived CD81 decreased eNOS expression in endothelial cell and increased the ability of endothelial cell permeability. Furthermore, we revealed that downregulation of eNOS expression by trophoblast-derived CD81 may occur partly through the PI3K/PDK1/Akt pathway.
Source: Intelligent Pharmacy
Authors: Li Shen, Yujing Li, Dan Liu, Qiang Li
Institutions: Nanjing Drum Tower Hospital, Nanjing University
Language: English
Subfield: Obstetrics and Gynecology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,200
OpenAlex ID: W4417147453