MicroRNA-30d-5p ameliorates lipopolysaccharide-induced acute lung injury via activating AMPKα.

Acute lung injury (ALI) is a devastating lung disease characterized by uncontrolled pulmonary inflammation and oxidative stress. Currently, no effective therapeutic strategies are available for ALI and its prognosis remains poor. The present study aims to investigate the role and potential mechanism of microRNA-30d-5p (miR-30d-5p) in the progression of ALI. Mice were intravenously treated with miR-30d-5p agomir, antagomir or their respective controls for 3 consecutive days and then were exposed to a single intratracheal injection of lipopolysaccharide (LPS) for 12 h at a dosage of 5 mg/kg to induce ALI. To inhibit adenosine monophosphate-activated protein kinase α (AMPKα) or phosphodiesterase 4 D (PDE4D), compound C (CpC) and rolipram were used. miR-30d-5p expression in the lungs was significantly inhibited by LPS treatment. miR-30d-5p agomir significantly alleviated, while miR-30d-5p antagomir aggravated pulmonary inflammation, oxidative damage, and dysfunction in ALI mice. Besides, we found that miR-30d-5p agomir ameliorated LPS-induced ALI via activating AMPKα and that the inhibition of AMPKα by CpC completely abolished these beneficial effects of miR-30d-5p agomir. Further findings validated that PDE4D downregulation was required for the activation of AMPKα by miR-30d-5p agomir. miR-30d-5p ameliorates LPS-induced ALI via activating AMPKα and it is a valuable therapeutic candidate in the treatment of ALI.