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Prophylactic treatment with MSC-derived exosomes attenuates traumatic acute lung injury in rats.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2019 Jun 01; Vol. 316 (6), pp. L1107-L1117. Date of Electronic Publication: 2019 Mar 20. - Publication Year :
- 2019
-
Abstract
- The mesenchymal stem cell (MSC) is a potential strategy in the pretreatment of traumatic acute lung injury (ALI), a disease that causes inflammation and oxidative stress. This study aimed to investigate whether MSC-exosomal microRNA-124-3p (miR-124-3p) affects traumatic ALI. Initially, a traumatic ALI rat model was established using the weight-drop method. Then, exosomes were obtained from MSCs of Sprague-Dawley rats, which were injected into the traumatic ALI rats. We found that miR-124-3p was abundantly-expressed in MSCs-derived exosomes and could directly target purinergic receptor P2X ligand-gated ion channel 7 (P2X7), which was overexpressed in traumatic ALI rats. After that, a loss- and gain-of-function study was performed in MSCs and traumatic ALI rats to investigate the role of miR-124-3p and P2X7 in traumatic ALI. MSC-derived exosomal miR-124-3p or silenced P2X7 was observed to increase the survival rate of traumatic ALI rats and enhance the glutathione/superoxide dismutase activity in their lung tissues. However, the wet/dry weight of lung tissues, activity of methylenedioxyamphetamine and H <subscript>2</subscript> O <subscript>2</subscript> , and levels of inflammatory factors (TNF-a, IL-6, and IL-8) were reduced. Similarly, the numbers of total cells, macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage fluid were also reduced when treated with exosomal miR-124-3p or silenced P2X7. In conclusion, the results provide evidence that miR-124-3p transferred by MSC-derived exosomes inhibited P2X7 expression, thus improving oxidative stress injury and suppressing inflammatory response in traumatic ALI, highlighting a potential pretreatment for traumatic ALI.
- Subjects :
- Animals
Bronchoalveolar Lavage Fluid cytology
Cells, Cultured
Dioxoles metabolism
Disease Models, Animal
Hydrogen Peroxide metabolism
Interleukin-6 metabolism
Interleukin-8 metabolism
Male
MicroRNAs genetics
Rats
Rats, Sprague-Dawley
Tumor Necrosis Factor-alpha metabolism
Acute Lung Injury therapy
Exosomes genetics
Mesenchymal Stem Cells cytology
MicroRNAs pharmacology
Purinergic P2X Receptor Antagonists pharmacology
Receptors, Purinergic P2X7 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-1504
- Volume :
- 316
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 30892077
- Full Text :
- https://doi.org/10.1152/ajplung.00391.2018