Exosomal MicroRNA-328 from Bone Marrow Mesenchymal Stem Cells (BMSCs) Alleviates Acute Lung Injury Through Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase (MAPK/ERK) Pathway

Abstract

To elucidate the communication between exosomes (exo) derived from BMSCs and injured lung cells. BMSC-exo was isolated and characterized. Lung epithelial cells A549 were incubated with BMSC-exo, and treated by LPS to induce cell damage. CCK-8 assay was carried out to test cell proliferation, flow cytometry was adopted to analyze cell apoptosis, and RT-qPCR as well as Western blot analysis were selected to assess expression of apoptosis- and anti-apoptosis related proteins. Functional experiment was performed to identify the role of microRNA (miRNA)-328 in lung injury. LPS treatment significantly inhibited the viability of A549 cells, induced apoptosis of A549 cells by increasing Bax and casepase-3 levels and reducing Bcl-2 expression, whilst declined expression of miR-328 and suppressed the phosphorylation activation of the MAPK/ERK pathway. Meanwhile, the amount of IL-6, IL-1β and TNF-α were elevated in injured cells, but, the presence of BMSC-exo eliminated the elevation of the contents. Importantly, treatment with BMSC-exo increased miR-328 expression, activated MAPK MAPK/ERK pathway, inhibited apoptosis, and enhanced cell proliferation. However, the effect of BMSC-exo was attenuated when the cells were silenced for miR-328 expression. Collectively, BMSC-exo enriched miR-328 could relieve acute lung injury through MAPK/ERK pathway.