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

Abstract

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.

Value of foetal umbilical vein standardised blood flow volume in predicting weight gain in the third trimester: a prospective case-cohort study

“…Blood flow volume represents the physical aspect of foetal blood access. However, various biochemical substances in the blood play crucial roles as biological and chemical factors for foetal blood and nutrient acquisition, including vascular growth factors and blood sugar ( 32 , 33 ). Scholars from different countries have investigated the biochemical substances in foetal umbilical vein blood flow and concluded that multiple biochemical substances jointly affect foetal weight gain ( 34 ).…”

Connection between Radiation-Regulating Functions of Natural Products and miRNAs Targeting Radiomodulation and Exosome Biogenesis

“…As mentioned above, most radiation-modulating natural-product-regulated miRNAs (Table 3) are associated with exosome biogenesis and miRDB results for exosome biogenesismodulating targets. However, other miRNAs , such as miR-3960 [143], miR-6085 [144], miR-18a-5p [145], miR-22-3p [146], miR-126-3p [147], miR-137-3p [148], miR-122-5p [149], miR-23a-3p [150], miR-155-5p [151], miR-33a-5p [152], miR-574-3p [153], miR-132-3p [154], miR-211-5p [155], miR-375-3p [156], miR-181c-3p [157], miR-146a-5p [158], miR-542-3p [159], miR-877-3p [160], miR-192-5p [161], miR-451a [162], miR-215-5p [163], miR-99b-3p [164], miR-549a-5p [165], and miR-1247-5p [166], have only been reported in terms of exosome biogenesis-modulating effects, without available miRDB results for exosome biogenesis-modulating targets.…”

“…Exosomal miR-33a-5p was present at only a low level in resistant colon cancer cells [152]. Placenta-derived exosomal miR-574-3p was underexpressed after chemerin, enhancing proliferation and angiogenesis for gestational diabetes mellitus [153]. Mesenchymal stem-cell-derived exosomal miR-132-3p improved proliferation, inhibited apoptosis in an in vitro inflammatory cell model, and reduced LPS-induced acute lung injury in mice [154].…”