Bone marrow mesenchymal stem cell-conditioned medium facilitates fluid resolution via miR-214-activating epithelial...

Acute lung injury (ALI) is featured with severe lung edema at the early exudative phase, resulting from the imbalance of alveolar fluid turnover and clearance. Mesenchymal stem cells (MSCs) belong to multipotent stem cells, which have shown potential therapeutic effects during ALI. Of note, MSC-conditioned medium (MSC-CM) improved alveolar fluid clearance (AFC) in vivo, whereas the involvement of miRNAs is seldom known. We thus aim to explore the roles of miR-214 in facilitating MSC-CM mediated fluid resolution of impaired AFC. In this study, AFC was increased significantly by intratracheally administrated MSC-CM in lipopolysaccharide-treated mice. MSC-CM augmented amiloride-sensitive currents in intact H441 monolayers, and increased α-epithelial sodium channel (α-ENaC) expression level in H441 and mouse alveolar type 2 epithelial cells. Meanwhile, MSC-CM increased the expression of miR-214, which may participate in regulating ENaC expression and function. Our results suggested that MSC-CM enhanced AFC in ALI mice in vivo through a novel mechanism, involving miR-214 regulation of ENaC.