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The Pro-angiogenesis Of Exosomes Derived From Umbilical Cord Blood Of Intrauterine Growth Restriction Pigs Was Repressed Associated With MiRNAs.

ABSTRACT: Dysfunctional umbilical cord blood (UCB) is a key factor for the development of intrauterine growth restriction (IUGR) in utero. Poor degrees of angiogenesis were observed during IUGR development. Here, it was demonstrated that NV-EXO (normal piglet's Umbilical Veins derived exosomes) promoted angiogenesis within the subdued pro-angiogenesis context of IV-EXO (IUGR piglet's Umbilical Veins derived exosomes). Investigation of the miRNA transcriptome of umbilical cord vein and artery exosomes between IUGR and normal littermates showed significant differences between umbilical veins from normal (NV) and IUGR (IV) piglets. Similar patterns were observed in normal (NA) and IUGR (IA) umbilical arteries as well. Moreover, the miRNAs expession level was more stable in NV. Further analysis revealed that miRNAs related to angiogenesis exhibited aberrant expression in IUGR pigs. The miRNA expression patterns between IUGR and normal piglets showed great difference. Expression of miR-150 in the tissues and UCB exosomes of IUGR pigs was significantly decreased. Up-regulation of miR-150 was able to increase proliferation, migration and tube formation of Human umbilical vein endothelial cells (HUVECs), suggesting a pro-angiogenic role. Furthermore, the data demonstrated that UCB derived miRNAs participate in fetal epigenetic regulation during pregnancy, suggesting a novel possible explanation for abnormal embryologic vascular development and several congenital cardiovascular diseases.

SUBMITTER: Luo J

PROVIDER: S-EPMC6158734 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The Pro-angiogenesis Of Exosomes Derived From Umbilical Cord Blood Of Intrauterine Growth Restriction Pigs Was Repressed Associated With MiRNAs.

Luo Jia J Fan Yuan Y Shen Linyuan L Niu LiLi L Zhao Ye Y Jiang Dongmei D Zhu Lin L Jiang An'an A Tang Qianzi Q Ma Jideng J Jin Long L Wang Jinyong J Li Xuewei X Zhang Shunhua S Zhu Li L

International journal of biological sciences 20180806 11

Dysfunctional umbilical cord blood (UCB) is a key factor for the development of intrauterine growth restriction (IUGR) <i>in utero</i>. Poor degrees of angiogenesis were observed during IUGR development. Here, it was demonstrated that NV-EXO (normal piglet's Umbilical Veins derived exosomes) promoted angiogenesis within the subdued pro-angiogenesis context of IV-EXO (IUGR piglet's Umbilical Veins derived exosomes). Investigation of the miRNA transcriptome of umbilical cord vein and artery exosom ...[more]

PMID: 30262994

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Project description:The application of blood plasma for soft tissue wound healing is receiving much more attention recently. Exosomes are critical paracrine mediators that can be obtained from biological fluids including plasma and be able to induce regenerative effects by transferring bioactive molecules such as microRNAs (miRNAs). This study aimed to investigate the effects of exosomes from human umbilical cord blood plasma (UCB-Exos) on wound healing and to elucidate the underlying mechanism. Methods: UCB-Exos were isolated by ultracentrifugation and subcutaneously injected into full-thickness skin wounds in mice. The efficacy of UCB-Exos on wound healing was evaluated by measuring wound closure rates, histological analysis and immunofluorescence examinations. In vitro, quantitative real-time PCR (qRT-PCR) analysis was performed to detect the expression levels of a class of miRNAs that have positive roles in regulating wound healing. The scratch wound assay, transwell assay and cell counting kit-8 analysis were conducted to assess the effects of UCB-Exos on migration and proliferation of human skin fibroblasts and endothelial cells. Tube formation assay was carried out to test the impact of UCB-Exos on angiogenic tube formation ability of endothelial cells. Meanwhile, by using specific RNA inhibitors or siRNAs, the roles of the candidate miRNA and its target genes in UCB-Exos-induced regulation of function of fibroblasts and endothelial cells were assessed. Results: The local transplantation of UCB-Exos into mouse skin wounds resulted in accelerated re-epithelialization, reduced scar widths, and enhanced angiogenesis. In vitro, UCB-Exos could promote the proliferation and migration of fibroblasts, and enhance the angiogenic activities of endothelial cells. Notably, miR-21-3p was found to be highly enriched in UCB-Exos and served as a critical mediator in UCB-Exos -induced regulatory effects through inhibition of phosphatase and tensin homolog (PTEN) and sprouty homolog 1 (SPRY1). Conclusion: Our results suggest that UCB-Exos are important effectors of plasma activity and can be used as a novel promising strategy for soft tissue wound healing.

Dataset Information

The Pro-angiogenesis Of Exosomes Derived From Umbilical Cord Blood Of Intrauterine Growth Restriction Pigs Was Repressed Associated With MiRNAs.

Publications

The Pro-angiogenesis Of Exosomes Derived From Umbilical Cord Blood Of Intrauterine Growth Restriction Pigs Was Repressed Associated With MiRNAs.

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