Exosomal encapsulation of miR-125a-5p inhibited trophoblast cell migration and proliferation by regulating the expression of VEGFA in preeclampsia

Zhao, Xueya; Li, Yamei; Chen, Sha; Chen, Dan; Shen, Hong; Yang, Xingyu; Cheng, Weiwei

doi:10.1016/j.bbrc.2020.02.137

Cited by 55 publications

(38 citation statements)

References 33 publications

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“…MSC‐originated exosomes overexpressing H19 reduced let‐7b and strengthened forkhead box protein O1 (FOXO1) expression to trigger the protein kinase B (AKT) pathway, thus enhancing trophoblast activities 8 . A report summarized the exo‐miRNA of umbilical cord blood in healthy and PE pregnant females systematically and validated that miR‐125a‐5p dysregulation might influence HTR8/SVneo cell angiogenesis, which is an indicative of miR‐125a‐5p involvement throughout PE progression 10 . Placenta‐connected serum exosomes could constrain expression of endothelial nitric oxide synthase during PE progression in endothelial cells, and this occurrence may be fairly caused by raised miR‐155 expression in the exosomes 25 .…”

Section: Discussionmentioning

confidence: 97%

“…8 A report summarized the exo-miRNA of umbilical cord blood in healthy and PE pregnant females systematically and validated that miR-125a-5p dysregulation might influence HTR8/SVneo cell angiogenesis, which is an indicative of miR-125a-5p involvement throughout PE progression. 10 Placenta-connected serum exosomes could constrain expression of endothelial nitric oxide synthase during PE progression in endothelial cells, and this occurrence may be fairly caused by raised miR-155 expression in the exosomes. 25 Besides, MSC-derived exosomal miR-146a-5p and miR-548e-5p possess antiinflammatory capability on human trophoblasts and were suggested to be innovative targets for healing inflammatory-associated diseases during pregnancy, such as PE.…”

Section: Ameliorative Effect Of Exosomes On Pe Ratsmentioning

confidence: 99%

“…9 miRNA play an essential role in placental-related disorders by binding to the 3 0 -untranslated region of target mRNA, thus hindering the expression of target mRNA. 10 microRNA-139-5p (miR-139-5p) is positioned in the human chromosome 11q13.4 region, 11 which has been recognized as a tumorconquering miRNA due to its downregulation in numerous types of tumor, such as non-small cell lung, prostate and breast cancers. [12][13][14] Interestingly, a study uncovered the function of miR-139-5p in trophoblasts by regulating soluble fms-like tyrosine kinase-1 in PE.…”

Section: Introductionmentioning

confidence: 99%

“…Interestingly, around 60% of the circulating microRNAs (miRNA) is linked with exosomes, and the miRNA in exosomes are resilient to RNase management 9 . miRNA play an essential role in placental‐related disorders by binding to the 3′‐untranslated region of target mRNA, thus hindering the expression of target mRNA 10 . microRNA‐139‐5p (miR‐139‐5p) is positioned in the human chromosome 11q13.4 region, 11 which has been recognized as a tumor‐conquering miRNA due to its downregulation in numerous types of tumor, such as non‐small cell lung, prostate and breast cancers 12–14 .…”

Section: Introductionmentioning

confidence: 99%

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Exosomal microRNA‐139‐5p from mesenchymal stem cells accelerates trophoblast cell invasion and migration by motivation of the ERK/MMP‐2 pathway via downregulation of protein tyrosine phosphatase

Liu

Wang²,

Zhang³

et al. 2020

J of Obstet and Gynaecol

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Aim: Exosomes present essential roles for intercellular interaction via extracellular pathways during systemic dysfunctions, including preeclampsia (PE). Here, we assessed the specific mechanism of mesenchymal stem cells (MSC)-originated exosomes in PE. Methods: The effects of exosomes on trophoblasts were studied by EdU, wound healing, Transwell and TUNEL assays. By microarray analysis, we found that exosomes enhanced the microRNA-139-5p (miR-139-5p) in trophoblasts, and confirmed the target gene of miR-139-5p by bioinformatics prediction and dualluciferase reporter gene assay. At the same time, ERK/MMP-2 pathway-related biomolecules were assessed through Western blot analysis. The pathway inhibitor was used for rescue experiments. Finally, the effect of exosomes on the pathology of PE rats was verified by in vivo experiments. Results: The exosomes originated from hucMSC fostered the trophoblast cell migration, invasion and proliferation and obstructed apoptosis. Moreover, miR-139-5p could be transmitted to trophoblasts through hucMSC-secreted exosomes. miR-139-5p targeted protein tyrosine phosphatase (PTEN), which regulated the ERK/MMP-2 pathway. Inhibition of the ERK/MMP-2 pathway significantly reduced the promoting effect of exosomes on trophoblasts. Treatment with exosomes significantly lowered blood pressure values and reduced 24-h proteinuria in PE rats. Conclusion: hucMSC-originated exosomes overexpressing miR-139-5p activated the ERK/MMP-2 pathway via PTEN downregulation, thus accelerating trophoblast cell invasion and migration, and blocking apoptosis. These results demonstrated that hucMSC-derived exosomes overexpressing miR-139-5p might be an innovative direction for therapeutic approaches against PE.

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Section: Discussionmentioning

confidence: 97%

Section: Ameliorative Effect Of Exosomes On Pe Ratsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Exosomal microRNA‐139‐5p from mesenchymal stem cells accelerates trophoblast cell invasion and migration by motivation of the ERK/MMP‐2 pathway via downregulation of protein tyrosine phosphatase

Liu

Wang²,

Zhang³

et al. 2020

J of Obstet and Gynaecol

View full text Add to dashboard Cite

show abstract

“…Moreover, exosomal miR-125a, isolated from human adipose-derived MSCs, could be taken up by endothelial cells leading to enhanced angiogenesis both in vitro and in vivo by repressing angiogenic inhibitor delta-like 4 (DLL4) [ 228 ]. Conversely, over-expression of miR-125a-5p in human trophoblast cells resulted in decreased cell migration and inhibited angiogenesis through decreased VEGFA expression [ 229 ].…”

Section: Circulating and Tissue Micrornas As Biomarkers For The Eamentioning

confidence: 99%

Mechanistic Actions of microRNAs in Diabetic Wound Healing

Petković

Sørensen

Leal

et al. 2020

Cells

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Wound healing is a complex biological process that is impaired under diabetes conditions. Chronic non-healing wounds in diabetes are some of the most expensive healthcare expenditures worldwide. Early diagnosis and efficacious treatment strategies are needed. microRNAs (miRNAs), a class of 18–25 nucleotide long RNAs, are important regulatory molecules involved in gene expression regulation and in the repression of translation, controlling protein expression in health and disease. Recently, miRNAs have emerged as critical players in impaired wound healing and could be targets for potential therapies for non-healing wounds. Here, we review and discuss the mechanistic background of miRNA actions in chronic wounds that can shed the light on their utilization as specific wound healing biomarkers.

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