Background
Paraquat (PQ) presents with high toxicity for humans and animals, and the lungs become the main target organ by the poisoning of PQ leading to acute lung injury. Endothelial progenitor cells (EPCs) were proved to have the repair function on acute lung injury (ALI). We aimed to invatigate the underlying mechanism of EPCs in PQ-induced ALI involving miR-141-3p.
Conclusions
Endothelial progenitor cells could provide therapeutic effect on PQ-induced ALI via miR-141-3p-Notch-Nrf2 Axis.
Methods
Endothelial progenitor cells were isolated from peripheral blood of C57BL/6J mice and identified by flow cytometry. Lung wet-to-dry (W/D) weight ratios, lung injury score and the number of total leukocyte and the number of neutrophils in BALF were used to analyze the degree of lung injury. The transfection was performed with Lipofectamine 2000. The levels of miRNA and mRNA were determined by qRT-PCR, and the protein levels were detected by Western blot assay.
Results
Endothelial progenitor cells alleviated lung wet-to-dry (W/D) weight ratios, lung injury score and the number of total leukocyte and the number of neutrophils in BALF in PQ-induced ALI mice. EPCs inhibited miR-141-3p expression, and enhanced the levels of Notch-Nrf2 axis in PQ-induced ALI mice. MiR-141-3p knockdown reversed the PQ induced-inhibition on Notch-1 and Hesr1 expression. MiR-141-3p over-expression could inhibit the expression of Notch-1 pathway significantly in the pulmonary epithelial cell line MLE-12. Both miR-141-3p over-expression and si-Notch-1 abolished the protection effect of EPCs on lung injury induced by PQ in vivo. Conclusions: Endothelial progenitor cells could provide therapeutic effect on PQ-induced ALI via miR-141-3p-Notch-Nrf2 Axis.