Chemerin-Induced Down-Regulation of Placenta-Derived Exosomal miR-140-3p and miR-574-3p Promotes Umbilical Vein Endothelial Cells Proliferation, Migration, and Tube Formation in Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes and fetoplacental endothelial dysfunction; however, the underlying mechanisms remain unknown. This study aimed to investigate the effect of placenta-derived exosomal miRNAs on fetoplacental endothelial dysfunction in GDM, as well a...

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Main Authors: Lixia Zhang, Qi Wu, Shuqi Zhu, Yibo Tang, Yanmin Chen, Danqing Chen, Zhaoxia Liang
Format: Article
Language:English
Published: MDPI AG 2022-11-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/21/3457
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author Lixia Zhang
Qi Wu
Shuqi Zhu
Yibo Tang
Yanmin Chen
Danqing Chen
Zhaoxia Liang
author_facet Lixia Zhang
Qi Wu
Shuqi Zhu
Yibo Tang
Yanmin Chen
Danqing Chen
Zhaoxia Liang
author_sort Lixia Zhang
collection DOAJ
description Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes and fetoplacental endothelial dysfunction; however, the underlying mechanisms remain unknown. This study aimed to investigate the effect of placenta-derived exosomal miRNAs on fetoplacental endothelial dysfunction in GDM, as well as to further explore the role of chemerin to this end. Placenta-derived exosomal miR-140-3p and miR-574-3p expression (next-generation sequencing, quantitative real-time PCR), its interactions with cell function (Cell Counting Kit-8, Transwell, tube formation assay), chemerin interactions (Western blotting), and placental inflammation (immunofluorescence staining, enzyme-linked immunosorbent assay) were investigated. Placenta-derived exosomal miR-140-3p and miR-574-3p were downregulated in GDM. Additionally, miR-140-3p and miR-574-3p inhibited the proliferation, migration, and tube formation ability of umbilical vein endothelial cells by targeting vascular endothelial growth factor. Interestingly, miR-140-3p and miR-574-3p expression levels were negatively correlated with chemerin, which induced placental inflammation through the recruitment of macrophage cells and release of IL-18 and IL-1β. These findings indicate that chemerin reduces placenta-derived exosomal miR-140-3p and miR-574-3p levels by inducing placental inflammation, thereby promoting the proliferation, migration, and tube formation of umbilical vein endothelial cells in GDM, providing a novel perspective on the underlying pathogenesis and therapeutic targets for GDM and its offspring complications.
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spelling doaj.art-07c3c41a5961483d825d5860c84cfb7b2023-11-24T04:09:07ZengMDPI AGCells2073-44092022-11-011121345710.3390/cells11213457Chemerin-Induced Down-Regulation of Placenta-Derived Exosomal miR-140-3p and miR-574-3p Promotes Umbilical Vein Endothelial Cells Proliferation, Migration, and Tube Formation in Gestational Diabetes MellitusLixia Zhang0Qi Wu1Shuqi Zhu2Yibo Tang3Yanmin Chen4Danqing Chen5Zhaoxia Liang6Department of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaDepartment of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaDepartment of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaDepartment of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaDepartment of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaDepartment of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaDepartment of Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, ChinaGestational diabetes mellitus (GDM) leads to poor pregnancy outcomes and fetoplacental endothelial dysfunction; however, the underlying mechanisms remain unknown. This study aimed to investigate the effect of placenta-derived exosomal miRNAs on fetoplacental endothelial dysfunction in GDM, as well as to further explore the role of chemerin to this end. Placenta-derived exosomal miR-140-3p and miR-574-3p expression (next-generation sequencing, quantitative real-time PCR), its interactions with cell function (Cell Counting Kit-8, Transwell, tube formation assay), chemerin interactions (Western blotting), and placental inflammation (immunofluorescence staining, enzyme-linked immunosorbent assay) were investigated. Placenta-derived exosomal miR-140-3p and miR-574-3p were downregulated in GDM. Additionally, miR-140-3p and miR-574-3p inhibited the proliferation, migration, and tube formation ability of umbilical vein endothelial cells by targeting vascular endothelial growth factor. Interestingly, miR-140-3p and miR-574-3p expression levels were negatively correlated with chemerin, which induced placental inflammation through the recruitment of macrophage cells and release of IL-18 and IL-1β. These findings indicate that chemerin reduces placenta-derived exosomal miR-140-3p and miR-574-3p levels by inducing placental inflammation, thereby promoting the proliferation, migration, and tube formation of umbilical vein endothelial cells in GDM, providing a novel perspective on the underlying pathogenesis and therapeutic targets for GDM and its offspring complications.https://www.mdpi.com/2073-4409/11/21/3457placenta-derived exosomal miRNAschemerinumbilical vein endothelial cellsgestational diabetes mellitus
spellingShingle Lixia Zhang
Qi Wu
Shuqi Zhu
Yibo Tang
Yanmin Chen
Danqing Chen
Zhaoxia Liang
Chemerin-Induced Down-Regulation of Placenta-Derived Exosomal miR-140-3p and miR-574-3p Promotes Umbilical Vein Endothelial Cells Proliferation, Migration, and Tube Formation in Gestational Diabetes Mellitus
Cells
placenta-derived exosomal miRNAs
chemerin
umbilical vein endothelial cells
gestational diabetes mellitus
title Chemerin-Induced Down-Regulation of Placenta-Derived Exosomal miR-140-3p and miR-574-3p Promotes Umbilical Vein Endothelial Cells Proliferation, Migration, and Tube Formation in Gestational Diabetes Mellitus
title_full Chemerin-Induced Down-Regulation of Placenta-Derived Exosomal miR-140-3p and miR-574-3p Promotes Umbilical Vein Endothelial Cells Proliferation, Migration, and Tube Formation in Gestational Diabetes Mellitus
title_fullStr Chemerin-Induced Down-Regulation of Placenta-Derived Exosomal miR-140-3p and miR-574-3p Promotes Umbilical Vein Endothelial Cells Proliferation, Migration, and Tube Formation in Gestational Diabetes Mellitus
title_full_unstemmed Chemerin-Induced Down-Regulation of Placenta-Derived Exosomal miR-140-3p and miR-574-3p Promotes Umbilical Vein Endothelial Cells Proliferation, Migration, and Tube Formation in Gestational Diabetes Mellitus
title_short Chemerin-Induced Down-Regulation of Placenta-Derived Exosomal miR-140-3p and miR-574-3p Promotes Umbilical Vein Endothelial Cells Proliferation, Migration, and Tube Formation in Gestational Diabetes Mellitus
title_sort chemerin induced down regulation of placenta derived exosomal mir 140 3p and mir 574 3p promotes umbilical vein endothelial cells proliferation migration and tube formation in gestational diabetes mellitus
topic placenta-derived exosomal miRNAs
chemerin
umbilical vein endothelial cells
gestational diabetes mellitus
url https://www.mdpi.com/2073-4409/11/21/3457
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