MicroRNA-499-5p targets SIRT1 to aggravate lipopolysaccharide-induced acute lung injury.

Acute lung injury (ALI) is a life-threatening disease without effective and specific therapeutic strategies except the life-supporting treatments. Inflammation and oxidative stress are essential for the progression of ALI. MicroRNA-499-5p () has multiple pathophysiological actions; however, its function and mechanisms in ALI remain elusive. Mice were intravenously injected with agomir, antagomir or the negative controls for 3 consecutive days and then received a single intratracheal injection of lipopolysaccharide (LPS, 5 mg/kg) to generate ALI model. Twenty four hours prior to LPS injection, EX-527 (1 mg/kg) was applied to inhibit SIRT1 activity. We identified a significant upregulation of in LPS-treated lung tissues. antagomir prevented, while agomir promoted inflammation, oxidative stress and ALI in LPS-treated mice. Further studies indicated that directly bound to the 3'-untranslated region of Sirtuin 1 () and decreased its protein level. SIRT1 inhibition blocked antagomir-mediated pulmonary protection against LPS injury. targets SIRT1 to aggravate LPS-induced ALI and it is a promising therapeutic target for the treatment of ALI.