MicroRNA-206 antagomiR‒enriched extracellular vesicles attenuate lung ischemia‒reperfusion injury through CXCL1 regulation in alveolar epithelial cells
| Autor: | Zhenxiao Tu, Victoria Leroy, A. Pelaez, Ashish Sharma, Carl Atkinson, Tiago N. Machuca, Jun Cai, V. Mas, Gang Su, Junyi Shang, Ricardo C. Gehrau, Gilbert R. Upchurch, A. Emtiazjoo |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Chemokine CXCL1 medicine.medical_treatment 030230 surgery Lung injury Article Proinflammatory cytokine Mice 03 medical and health sciences 0302 clinical medicine Animals Humans Medicine Lung transplantation Transplantation Lung medicine.diagnostic_test business.industry Mesenchymal stem cell Antagomirs Lung Injury respiratory system medicine.disease respiratory tract diseases Mice Inbred C57BL CXCL1 Disease Models Animal MicroRNAs 030104 developmental biology Bronchoalveolar lavage medicine.anatomical_structure Gene Expression Regulation Reperfusion Injury Cancer research RNA Surgery Cardiology and Cardiovascular Medicine business Bronchoalveolar Lavage Fluid Reperfusion injury Lung Transplantation |
| Zdroj: | J Heart Lung Transplant |
| ISSN: | 1053-2498 |
| DOI: | 10.1016/j.healun.2020.09.012 |
| Popis: | BACKGROUND Our hypothesis is that the immunomodulatory capacities of mesenchymal stem cell‒derived extracellular vesicles (EVs) can be enhanced by specific microRNAs (miRNAs) to effectively attenuate post-transplant lung ischemia‒reperfusion (IR) injury. METHODS The expression of miR-206 was analyzed in bronchoalveolar lavage (BAL) fluid of patients on Days 0 and 1 after lung transplantation. Lung IR injury was evaluated in C57BL/6 mice using a left lung hilar-ligation model with or without treatment with EVs or antagomiR-206‒enriched EVs. Murine lung tissue was used for miRNA microarray hybridization analysis, and cytokine expression, lung injury, and edema were evaluated. A donation after circulatory death and murine orthotopic lung transplantation model was used to evaluate the protection by enriched EVs against lung IR injury. In vitro studies analyzed type II epithelial cell activation after coculturing with EVs. RESULTS A significant upregulation of miR-206 was observed in the BAL fluid of patients on Day 1 after lung transplantation compared with Day 0 and in murine lungs after IR injury compared with sham. Treatment with antagomiR-206‒enriched EVs attenuated lung dysfunction, injury, and edema compared with treatment with EVs alone after murine lung IR injury. Enriched EVs reduced lung injury and neutrophil infiltration as well as improved allograft oxygenation after murine orthotopic lung transplantation. Enriched EVs significantly decreased proinflammatory cytokines, especially epithelial cell‒dependent CXCL1 expression, in the in vivo and in vitro IR injury models. CONCLUSIONS EVs can be used as biomimetic nanovehicles for protective immunomodulation by enriching them with antagomiR-206 to mitigate epithelial cell activation and neutrophil infiltration in the lungs after IR injury. |
| Databáze: | OpenAIRE |
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