miR-27a protects against acute lung injury in LPS-treated mice by inhibiting NF-κB-mediated inflammatory response.

Acute lung injury (ALI), which is an excessive uncontrolled inflammatory response in the lung, is mediated by several pro-inflammatory mediators. Recent evidence has implicated microRNAs (miRNAs) in regulation of inflammation in different diseases. However, the roles and underlying molecular mechanism of miRNAs in ALI have not been adequately elucidated. Thus, the aim of the present study was to investigate the possible regulatory mechanism of miRNAs in ALI. In this study, microRNA microarray analysis showed that 48 miRNAs were differentially expressed in lung tissues of an ALI model induced by LPS. Downregulation of miR-27a, played a key role in the regulation of the inflammatory response and protection from traumatic injury. Functional analyses indicated that overexpression of miR-27a using miR-27a agomir (agomiR-27a) protected the animals from LPS-induced ALI through decreased pulmonary inflammation, decreased wet-to-dry weight ratio, and ameliorated lung histopathological changes. In addition, agomiR-27a also decreased production of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF). Moreover, transforming growth factor β-activated kinase 1 binding protein 3 (TAB3), as an activator of NF-κB, was confirmed as a direct target of miR-27a. Further study showed that the anti-inflammatory mechanism of miR-27a is exerted via suppression NF-κB signaling by inhibiting expression of TAB3 in LPS-induced ALI mice. Taken together, these data define the protective mechanism of miR-27a via inhibition of the inflammatory response through blocking NF-κB pathway. Therefore, miR-27a/TAB3/NF-κB axis may be therapeutically targeted to repress inflammation following ALI in the future.