Microrna-31-5p Exacerbates Lipopolysaccharide-Induced Acute Lung Injury Via Inactivating Cab39/Ampk Alpha Pathway

Acute lung injury (ALI) and the subsequent acute respiratory distress syndrome remain devastating diseases with high mortality rates and poor prognoses among patients in intensive care units. The present study is aimed at investigating the role and underlying mechanisms of microRNA-31-5p (miR-31-5p) on lipopolysaccharide- (LPS-) induced ALI. Mice were pretreated withmiR-31-5pagomir, antagomir, and their negative controls at indicated doses for 3 consecutive days, and then they received a single intratracheal injection of LPS (5 mg/kg) for 12 h to induce ALI. MH-S murine alveolar macrophage cell lines were cultured to further verify the role ofmiR-31-5pin vitro. For AMP-activated protein kinase alpha(AMPK alpha) and calcium-binding protein 39 (Cab39) inhibition, compound C or lentiviral vectors were used in vivo and in vitro. We observed an upregulation ofmiR-31-5pin lung tissue upon LPS injection.miR-31-5pantagomir alleviated, whilemiR-31-5pagomir exacerbated LPS-induced inflammation, oxidative damage, and pulmonary dysfunction in vivo and in vitro. Mechanistically,miR-31-5pantagomir activated AMPK alpha to exert the protective effects that were abrogated by AMPK alpha inhibition. Further studies revealed that Cab39 was required for AMPK alpha activation and pulmonary protection bymiR-31-5pantagomir. We provide the evidence that endogenousmiR-31-5pis a key pathogenic factor for inflammation and oxidative damage during LPS-induced ALI, which is related to Cab39-dependent inhibition of AMPK alpha.