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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2022-11-01
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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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