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Digestive Diseases and Sciences

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15-02-2024 | Pregnancy Cholestasis | Original Article

Exosomes from Intrahepatic Cholestasis of Pregnancy Induce Cell Apoptosis Through the miRNA-6891-5p/YWHAE Pathway

Authors: Ningzhen Ye, Xinrui Shi, Jianyi Gao, Ruirui Dong, Gaoying Wang, Jing Wang, Liang Luo, Ting Zhang

Published in: Digestive Diseases and Sciences | Issue 4/2024

Abstract

Background

Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse pregnancy outcomes; however, the underlying mechanisms are not fully understood.

Aims

This study aimed to determine the role of exosomal miR-6891-5p in placental trophoblast dysfunction in ICP and identify new biomarkers for ICP diagnosis.

Methods

Serum samples were collected from ICP patients and healthy pregnant women, and serum exosomes were extracted and identified. Fluorescent dye labeling of exosomes and cell-verified cell phagocytosis were performed. In vitro experiments were conducted by adding taurocholic acid to simulate the ICP environment. Cell proliferation and apoptosis levels were detected using flow cytometry and the cell counting kit-8 assay. Mimics were constructed to overexpress miR-6891-5p in cells, and the binding site between miR-6891-5p and YWHAE was verified using luciferase reporter genes.

Results

miR-6891-5p expression was significantly decreased in serum exosomes of ICP patients. Co-culturing with exosomes derived from ICP patients’ serum (ICP-Exos) decreased HTR-8/SVeno cell proliferation and increased apoptosis levels. miR-6891-5p upregulation in HTR-8/SVeno cells significantly increased cell viability and reduced cell apoptosis levels, as determined by the cell counting kit-8 assay and flow cytometry. A double luciferase assay confirmed that miR-6891-5p affected the expression of the downstream YWHAE protein.

Conclusions

This study indicates that serum exosomes from ICP patients can impact the apoptosis of placental trophoblast HTR-8/SVeno cells through the miR-6891-5P/YWHAE pathway and can serve as specific molecular markers for ICP diagnosis.

Graphical Abstract

Available only for authorised users

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Title: Exosomes from Intrahepatic Cholestasis of Pregnancy Induce Cell Apoptosis Through the miRNA-6891-5p/YWHAE Pathway
Authors: Ningzhen Ye
Xinrui Shi
Jianyi Gao
Ruirui Dong
Gaoying Wang
Jing Wang
Liang Luo
Ting Zhang
Publication date: 15-02-2024
Publisher: Springer US
Keyword: Pregnancy Cholestasis
Published in: Digestive Diseases and Sciences / Issue 4/2024
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-023-08265-w

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Abstract

Background

Aims

Methods

Results

Conclusions

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