MicroRNA-326 prevents sepsis-induced acute lung injury via targeting TLR4
Zhengjun Wang, Jie Yan, Fan Yang, Dengyun Wang, Yuan Lü, Li Liu
Abstract
Unrestrained inflammation provokes oxidative stress and contributes to the development of sepsis-induced acute lung injury (ALI). MicroRNA-326 (miR-326) is originally identified as an autoimmunity-associated microRNA, yet its role and potential molecular basis in sepsis-induced ALI remain unclear. Herein, we found that miR-326 was downregulated in murine lungs and macrophages upon lipopolysaccharide (LPS) stimulation. MiR-326 agomir prevented, whereas miR-326 antagomir exacerbated LPS-induced inflammation, oxidative stress, and ALI in mice. Furthermore, we found that miR-326 suppressed LPS-induced inflammation and oxidative stress in macrophages via downregulating toll-like receptor (TLR4), and TLR4 inhibition abolished miR-326 antagomir-mediated deleterious effect in vivo and in vitro. Finally, we proved miR-326 agomir notably alleviated sepsis-induced ALI after caecal ligation and puncture surgery. Our data identified miR-326 as a potential therapeutic target for sepsis-induced ALI.