دورية أكاديمية
Mesenchymal stromal/stem cells modulate response to experimental sepsis-induced lung injury via regulation of miR-27a-5p in recipient mice
| العنوان: | Mesenchymal stromal/stem cells modulate response to experimental sepsis-induced lung injury via regulation of miR-27a-5p in recipient mice |
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| المؤلفون: | Younes, Nadim, Zhou, Louis, Amatullah, Hajera, Mei, Shirley H J, Herrero, Raquel, Lorente, Jose Angel, Stewart, Duncan J, Marsden, Philip, Liles, W Conrad, Hu, Pingzhao, dos Santos, Claudia C |
| المصدر: | Thorax, 75(7):556-567 |
| سنة النشر: | 2020 |
| المجموعة: | Publisso (ZB MED-Publikationsportal Lebenswissenschaften) |
| مصطلحات موضوعية: | respiratory infection, ARDS, critical care |
| الوصف: | INTRODUCTION: Mesenchymal stromal cell (MSC) therapy mitigates lung injury and improves survival in murine models of sepsis. Precise mechanisms of therapeutic benefit remain poorly understood. OBJECTIVES: To identify host-derived regulatory elements that may contribute to the therapeutic effects of MSCs, we profiled the microRNAome (miRNAome) and transcriptome of lungs from mice randomised to experimental polymicrobial sepsis-induced lung injury treated with either placebo or MSCs. METHODS: and results A total of 11 997 genes and 357 microRNAs (miRNAs) expressed in lungs were used to generate a statistical estimate of association between miRNAs and their putative mRNA targets; 1395 miRNA:mRNA significant association pairs were found to be differentially expressed (false discovery rate ≤0.05). MSC administration resulted in the downregulation of miR-27a-5p and upregulation of its putative target gene VAV3 (adjusted p=1.272E-161) in septic lungs. In human pulmonary microvascular endothelial cells, miR-27a-5p expression levels were increased while VAV3 was decreased following lipopolysaccharide (LPS) or tumour necrosis factor (TNF) stimulation. Transfection of miR-27a-5p mimic or inhibitor resulted in increased or decreased VAV3 message, respectively. Luciferase reporter assay demonstrated specific binding of miR-27a-5p to the 3′UTR of VAV3. miR27a-5p inhibition mitigated TNF-induced (1) delayed wound closure, increased (2) adhesion and (3) transendothelial migration but did not alter permeability. In vivo, cell infiltration was attenuated by intratracheal coinstillation of the miR-27a-5p inhibitor, but this did not protect against endotoxin-induced oedema formation. CONCLUSIONS: Our data support involvement of miR-27a-5p and VAV3 in cellular adhesion and infiltration during acute lung injury and a potential role for miR-27a-based therapeutics for acute respiratory distress syndrome. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://repository.publisso.de/resource/frl:6424948Test; http://dx.doi.org/10.1136/thoraxjnl-2019-213561Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361025Test/ |
| DOI: | 10.1136/thoraxjnl-2019-213561 |
| الإتاحة: | https://doi.org/10.1136/thoraxjnl-2019-213561Test https://repository.publisso.de/resource/frl:6424948Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361025Test/ |
| حقوق: | http://creativecommons.org/licenses/by-nc/4.0Test/ |
| رقم الانضمام: | edsbas.2B05576F |
| قاعدة البيانات: | BASE |
| DOI: | 10.1136/thoraxjnl-2019-213561 |
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