Abstract
BackgroundBone 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 methodsThe 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.ResultsEPCs 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.ConclusionEPC 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.
Highlights
Sepsis, characterized by the activation of inflammation and coagulation and inhibition of fibrinolysis, is a major public health problem worldwide
endothelial progenitor cells (EPCs) increased the expression of miR-10a/b-5p and reduced ADAM15 protein level in LPS-induced acute lung injury (ALI) lung tissues and mouse pulmonary microvascular endothelial cells (MPMVECs) (p < 0.05), and promoted LPS-induced MPMVEC proliferation (p < 0.05)
EPC transplantation exerted its therapeutic effect of ALI via increasing miR-10a/b-5p and reducing ADAM15, providing a novel insight into the molecular mechanism of EPC transplantation in treating ALI
Summary
Sepsis, characterized by the activation of inflammation and coagulation and inhibition of fibrinolysis, is a major public health problem worldwide. Acute lung injury (ALI) is primarily caused by sepsis concerning both pulmonary and nonpulmonary infections, and is characterized by tachypnea and hypoxemia, which often progresses to respiratory failure requiring intubation and mechanical ventilation [2]. Bone marrow-derived endothelial progenitor cells (EPCs), shown to participate in physiologic and pathologic neovascularization, have been investigated as therapeutic. It has been reported that EPC transplantation can significantly reduce lung injury in septic mice and rats [9,10,11]. EPC transplantation has been demonstrated to attenuate LPSinduced lung injury in the animal models [12, 13], little is known about the underlying mechanisms. Bone marrow-derived endothelial progenitor cells (EPCs) are shown to attenuate lipopolysaccharide(LPS-) induced acute lung injury (ALI) in animal models.
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