Schematic diagram of the implicated signaling pathway relating to the proinflammatory effects of miR-92a on LPS-induced ALI. LPS can induce miR-92a upregulation in mice, and miR-92a then inhibits PTEN expression through targeting its 3ʹ-UTR, which activates the AKT/NF-κB signaling pathway. The activated AKT/NF-κB signaling pathway induces production of pro-inflammatory cytokines including IL-6, IL-1β and TNF-α, resulting in ALI in mice.

Overwhelming lung inflammation is a key feature of acute lung injury (ALI). MicroRNAs (miRNAs) have been implicated in the regulation diverse cellular processes including the inflammatory response. However, little is known about their functions and molecular involvement in regulating the inflammatory process in ALI. Herein, we established a lipopolysaccharide (LPS)-induced ALI mouse model and used miRNA microarray analysis to investigate and compare the miRNA expression profiles in mouse lung tissues. We found that miR-92a was markedly upregulated in the lung tissues of ALI mice compared with that in normal lung tissues. This upregulation of miR-92a in LPS-induced ALI mice was further confirmed in lung tissues, splenocytes and bronchoalveolar lavage fluid (BALF) by quantitative real-time PCR. Inhibition of miR-92a by injection with antagomir-92a markedly reduced LPS-induced pathological changes associated with lung inflammation, and reduces lung wet/dry ratio (W/D ratio), and Evans blue dye extravasation (an indicator of lung epithelial permeability). Moreover, inhibition of miR-92a ameliorated the inflammatory response by reducing the repression of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in lung tissues. In addition, we identified that miR-92a inhibited the phosphatase and tensin homolog on chromosome ten (PTEN) by binding to its 3ʹ-UTR in RAW264.7 murine macrophage cells. Western blot analysis demonstrated that inhibition of miR-92a may ameliorate inflammatory response through blocking PTEN/AKT/NF-κB signaling pathway in ALI mice. Collectively, these results have revealed a significant role of miR-92a in the lung inflammatory response associated with ALI in mice, and suggest that miR-92a may have potential as a prognostic indicator and novel therapeutic target for the treatment of ALI in future.