MiR-142a-3p alleviates Escherichia coli derived lipopolysaccharide-induced acute lung injury by targeting TAB2

Acute lung Injury (ALI) is the clinical syndrome of parenchymal lung disease, leading to an extremely high mortality. The pathogenesis of ALI is suggested to be a consequence of uncontrolled inflammation. Lipopolysaccharide (LPS)-induced ALI mice model is often used for the mechanism. Studies show that TGF-beta activated kinase 1 (MAP3K7) binding protein 1/2 (TAB2) plays a crucial role in LPS-induced inflammation response. Furthermore, microRNA-142a-3p (miR-142a-3p) has been observed to be involved in inflammation- induced disease. Thus, we investigated the role of miR-142a-3p and TAB2 on LPS-induced ALI, which involved the TLR4/TAB2/NF-kappa B signaling. ALI and normal lung tissues were collected to access the relative expression of pro-inflammatory cytokines and miR-142a-3p. Histopathological examination and Wet to Dry weight ratios of lung tissues were used to access the establishment of ALI models. Raw264.7 cells were transfected with si-TAB2 or miR-142a-3p mimics to elucidate the role of TAB2 or miR-142a-3p in the inflammatory cascade in ALI. Additionally, the relationship between miR-142a-3p and TAB2 was validated by dual-luciferase report system. Our study discovered that miR-142-3p was up-regulated both in LPS-induced ALI mice model and RAW264.7 cells model. MiR-142a-3p mimics group experienced significant decrease in the secretion of pro- inflammatory cytokines as a result of the inhibition of NFk B signaling pathway. Bioinformatics database showed that the adaptor protein, TAB2, was critical in this pathway and it is the target gene of miR-142a-3p. Their relation was first confirmed by us via dual-luciferase report system. Results of our study demonstrated that miR-142a-3p exerts as a protective role in LPS-induced ALI through down-regulation of NF-kappa B signaling pathway.