期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 852, 期 -, 页码 68-76出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2019.01.022
关键词
Ischemia/reperfusion injury; Mesenchymal stromal cells; Exosomes; miR-21-5p; Apoptosis
资金
- 23456 talent project of Henan Provincial People's Hospital
MiR-21-5p is an anti-apoptotic miRNA known to mediate the protective effect of mesenchymal stromal cell-secreted exosomes (MSC-Exo) against oxidative stress-induced cell death. In the present research we employed murine lung ischemia/reperfusion (I/R) model and in vitro hypoxia/reoxygenation (H/R) model using primary murine pulmonary endothelial cells to investigate whether MSC-Exo could alleviate lung IRI by transporting miR-21-5p. Our data suggested that intratracheal administration of MSC-Exo or miR-21-5p agomir significantly reduced lung edema and dysfunction, M1 polarization of alveolar macrophages as well as secretion of HMGB1, IL-8, IL-1 beta, IL-6, IL-17 and TNF-alpha. Pre-challenge of MSCs by H/R significant increased miR-21-5p expression level in exosomes they secreted and the anti-IRI effect of these MSC-Exo, while pre-treatment of MSCs with miR-21-5p antagomir showed opposite effect. We further demonstrated that MSC-Exo ameliorated IRI in vivo or H/R induced apoptosis in vitro by inhibiting both intrinsic and extrinsic apoptosis pathway via miR-21-5p targeting PTEN and PDCD4, while artificial overexpressing PTEN or PDCD4 significantly attenuated the anti-apoptotic effect of MSC-Exo in vitro. Treatment with miR-21-5p agomir mimicked the IRI-reducing and anti-apoptotic effect of MSC-Exo. Our data suggested that MSC-Exo alleviate IRI in lung in an exosomal miR-21-5p-dependent manner. Treatment with MSC-Exo or miR-21-5p agomir might ameliorate IRI in lung.
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