Background
Bone marrow-derived endothelial progenitor cells (EPCs) are shown to attenuate lipopolysaccharide- (LPS-) induced acute lung injury (ALI) in animal models. However, the molecular mechanism is largely unknown. Materials and
Conclusion
EPC transplantation exerted its therapeutic effect of ALI via increasing miR-10a/b-5p and reducing ADAM15, thus providing a novel insight into the molecular mechanism of EPC transplantation in treating ALI.
Methods
The animal model of ALI was induced by intratracheal instillation of purified LPS with 2.5 mg/ml/kg. The expression of microRNAs and ADAM15 in lung tissues and LPS-induced mouse pulmonary microvascular endothelial cells (MPMVECs) was determined by quantitative real-time PCR and western blot analysis. The target relationship between miR-10a/b-5p and ADAM15 was confirmed by luciferase reporter assay and RNA interference. The effect of EPCs on MPMVEC proliferation was detected by MTT assay.
Results
EPCs increased the expression of miR-10a/b-5p and reduced ADAM15 protein level in LPS-induced ALI lung tissues and MPMVECs (p < 0.05), and promoted LPS-induced MPMVEC proliferation (p < 0.05). ADAM15 was confirmed to be a downstream target of miR-10a/b-5p. Additionally, EPCs promoted LPS-induced MPMVEC proliferation and exerted the therapeutic effect of ALI via regulating miR-10a/b-5p/ADAM15 axis.