Extracellular vesicle‐enclosed miR‐486‐5p mediates wound healing with adipose‐derived stem cells by promoting angiogenesis

Lu, Yingjie; Wen, Huicai; Jing, Huang; Liao, Peng; Liao, Huaiwei; Tang, Jun; Zeng, Yanjun

doi:10.1111/jcmm.15387

Cited by 59 publications

(71 citation statements)

References 32 publications

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“…This suggests that smooth muscle cells could be the main receptor cells for miR-486 within the AVM context. Recent papers point out a role for miR-486 in the cardiovascular system, including angiogenesis and myocardial infarction [16,17], or even as a biomarker of cardiac pathologies such as bicuspid aortic disease [18]. Thus, we hypothesize that the increase in miR-486 in exosomes might alter the vascular remodeling, contributing to the development of AVM in HHT.…”

Section: Discussionmentioning

confidence: 84%

Identification of Exosomal MicroRNA Signature by Liquid Biopsy in Hereditary Hemorrhagic Telangiectasia Patients

Pozo-Agundo

Villaescusa

Martorell-Marugán

et al. 2021

IJMS

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Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant vascular dysplasia characterized by epistaxis, mucocutaneous telangiectases, and arteriovenous malformations (AVM) in the visceral organs. The diagnosis of HHT is based on clinical Curaçao criteria, which show limited sensitivity in children and young patients. Here, we carried out a liquid biopsy by which we isolated total RNA from plasma exosome samples. A cohort of 15 HHT type 1 patients, 15 HHT type 2 patients, and 10 healthy relatives were analyzed. Upon gene expression data processing and normalization, a statistical analysis was performed to explore similarities in microRNA expression patterns among samples and detect differentially expressed microRNAs between HHT samples and the control group. We found a disease-associated molecular fingerprint of 35 miRNAs over-represented in HHT vs. controls, with eight being specific for HHT1 and 11 for HHT2; we also found 30 under-represented, including nine distinct for HHT1 and nine for HHT2. The analysis of the receiver operating characteristic (ROC) curves showed that eight miRNAs had good (AUC > 75%) or excellent (AUC > 90%) diagnosis value for HHT and even for type HHT1 and HHT2. In addition, we identified the cellular origin of these miRNAs among the cell types involved in the vascular malformations. Interestingly, we found that only some of them were incorporated into exosomes, which suggests a key functional role of these exosomal miRNAs in the pathophysiology of HHT.

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Section: Discussionmentioning

confidence: 84%

Identification of Exosomal MicroRNA Signature by Liquid Biopsy in Hereditary Hemorrhagic Telangiectasia Patients

Pozo-Agundo

Villaescusa

Martorell-Marugán

et al. 2021

IJMS

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“…Studies have also shown an increase of miR-486-5p in patients with coronary artery disease ( Niculescu et al., 2015 ). More recently, miR-486-5p enriched in adipose-derived stem cell–EVs have been shown to accelerate the proliferation of skin fibroblasts ( Lu et al., 2020 ). Furthermore, miR-486-5p was shown to reduce ABCA-1 expression in macrophages ( Liu et al., 2016 ) that we reproduced through our studies of BMDM-HG-exo, which in this context could contribute to atherosclerosis acceleration in Apoe −/− mice treated with BMDM–HG-exo, and atherosclerosis in diabetic patients.…”

Section: Discussionmentioning

confidence: 99%

High glucose macrophage exosomes enhance atherosclerosis by driving cellular proliferation & hematopoiesis

et al. 2021

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Summary We investigated whether extracellular vesicles (EVs) produced under hyperglycemic conditions could communicate signaling to drive atherosclerosis. We did so by treating Apoe −/− mice with exosomes produced by bone marrow-derived macrophages (BMDM) exposed to high glucose (BMDM–HG-exo) or control. Infusions of BMDM–HG-exo increased hematopoiesis, circulating myeloid cell numbers, and atherosclerotic lesions with an accumulation of macrophage foam and apoptotic cells. Transcriptome-wide analysis of cultured macrophages treated with BMDM–HG-exo or plasma EVs isolated from subjects with type II diabetes revealed a reduced inflammatory state and increased metabolic activity. Furthermore, BMDM–HG-exo induced cell proliferation and reprogrammed energy metabolism by increasing glycolytic activity. Lastly, profiling microRNA in BMDM–HG-exo and plasma EVs from diabetic subjects with advanced atherosclerosis converged on miR-486-5p as commonly enriched and recognized in dysregulated hematopoiesis and Abca1 control. Together, our findings show that EVs serve to communicate detrimental properties of hyperglycemia to accelerate atherosclerosis in diabetes.

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“…MiR-22 could regulate endothelial angiogenesis, in ammation, and tissue injury by targeting vascular endothelial-cadherin [51]. MiR-486-5p released by adipose-derived stem cell-derived EV could mediate wound healing and promote angiogenesis [52]. MiR-21-5p could promote extracellular matrix degradation and angiogenesis in the unilateral anterior crossbite model [53].…”

Section: Discussionmentioning

confidence: 99%

Exosomes derived from bone marrow mesenchymal stem cells promote angiogenesis via transfer of miR-21-5p after cerebral ischemia in mice

Hu¹,

Hu²,

Liu³

et al. 2021

Preprint

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Background Mesenchymal stem cells (MSCs) transplantation is a potential clinical therapy for cerebral ischemia. The therapeutic effects of MSCs primarily depends on the paracrine action by releasing exosomes (Exos). Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) could modulate target cell functions by transferring microRNAs (miRs) cargo. In this study, we aimed to investigate whether BMSC-Exos could promote angiogenesis via transfer of miR-21-5p after cerebral ischemia. Methods BMSC-Exos were isolated from conditioned medium of BMSCs by differential ultracentrifugation, and confirmed by transmission electron microscopy, nanoparticle tracking analysis, and western blot analysis. In mice with middle cerebral artery occlusion (MCAO), the neurological function was evaluated by Zea Longa’s method, and the infarct volume and microvessel density were detected by TTC staining and vWF immunofluorescence staining, respectively. The proangiogenic effects of BMSC-Exos were assessed via proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro assays. The miR-21-5p expression was detected by qRT-PCR. The expression levels of VEGF, VEGFR2, Ang-1, and Tie-2 were determined by western blot. Results BMSC-Exos significantly improved neurological function and reduced infract volume after cerebral ischemia. Moreover, BMSC-Exos significantly upregulated the microvessel density and the expression levels of proangiogenic proteins VEGF, VEGFR2, Ang-1 and Tie-2 in the ischemic boundary region. MiR-21-5p expression was also dramatically increased after cerebral ischemia. In vitro assays revealed that BMSC-Exos enhanced HUVECs functions including proliferation, migration and tube formation, as well as increasing the expression of VEGF and VEGFR2. However, these proangiogenic effects of BMSC-Exos on HUVECs were reversed by miR-21-5p inhibitor. Conclusion Our study indicated that BMSC-Exos could promote angiogenesis and neurological function recovery via transfer of miR-21-5p. Therefore, the application of miR-21-5p-loaded BMSC-Exos might be an attractive treatment strategy of cerebral ischemia.

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Extracellular vesicle‐enclosed miR‐486‐5p mediates wound healing with adipose‐derived stem cells by promoting angiogenesis

Cited by 59 publications

References 32 publications

Identification of Exosomal MicroRNA Signature by Liquid Biopsy in Hereditary Hemorrhagic Telangiectasia Patients

Identification of Exosomal MicroRNA Signature by Liquid Biopsy in Hereditary Hemorrhagic Telangiectasia Patients

High glucose macrophage exosomes enhance atherosclerosis by driving cellular proliferation & hematopoiesis

Exosomes derived from bone marrow mesenchymal stem cells promote angiogenesis via transfer of miR-21-5p after cerebral ischemia in mice

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