Department of Animal Nutrition and Feed Science, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Key Laboratory of Swine Genetics and Breeding of Agricultural Ministry, Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Int J Mol Sci. 2021 Sep 26;22(19):10343. doi: 10.3390/ijms221910343.
Maternal obesity disrupts both placental angiogenesis and fetus development. However, the links between adipocytes and endothelial cells in maternal obesity are not fully understood. The aim of this study was to characterize exosome-enriched miRNA from obese sow's adipose tissue and evaluate the effect on angiogenesis of endothelial cells. Plasma exosomes were isolated and analyzed by nanoparticle tracking analysis (NTA), electron morphological analysis, and protein marker expression. The number of exosomes was increased as the gestation of the sows progressed. In addition, we found that exosomes derived from obese sows inhibited endothelial cell migration and angiogenesis. miRNA detection showed that miR-221, one of the miRNAs, was significantly enriched in exosomes from obese sows. Further study demonstrated that exosomal miR-221 inhibited the proliferation and angiogenesis of endothelial cells through repressing the expression of by targeting its 3' untranslated region. In summary, miR-221 was a key component of the adipocyte-secreted exosomal vesicles that mediate angiogenesis. Our study may be a novel mechanism showing the secretion of "harmful" exosomes from obesity adipose tissues causes placental dysplasia during gestation.
母体肥胖会破坏胎盘血管生成和胎儿发育。然而，母体肥胖中脂肪细胞与内皮细胞之间的联系尚未完全阐明。本研究旨在从肥胖母猪的脂肪组织中鉴定富含外泌体的 miRNA，并评估其对内皮细胞血管生成的影响。通过纳米颗粒跟踪分析（NTA）、电子形态分析和蛋白质标志物表达来分离和分析血浆外泌体。随着母猪妊娠的进展，外泌体的数量增加。此外，我们发现来自肥胖母猪的外泌体抑制了内皮细胞的迁移和血管生成。miRNA 检测表明，miR-221 是肥胖母猪外泌体中显著富集的 miRNA 之一。进一步的研究表明，外泌体 miR-221 通过靶向其 3'非翻译区来抑制内皮细胞的增殖和血管生成。总之，miR-221 是脂肪细胞分泌的外泌体小泡中的关键成分，介导血管生成。我们的研究可能揭示了肥胖脂肪组织分泌“有害”外泌体导致妊娠期胎盘发育不良的新机制。
