Effect and mechanism of long-chain noncoding RNA HOTAIR targeting micRNA-138 on inflammatory response and oxidative stress induced by LPS in septic rats

  Objective  To investigated the effect and mechanism of long-chain noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) targeting microRNA-138 (miRNA-138) and mediating Toll-like receptors 4 (TLR4)-dependent signaling pathway on inflammatory response and oxidative stress induced by lipopolysaccharide (LPS) in septic rats.

  Methods  Sixty male Sprague-Dawley rats were randomly divided into four groups according to body weight (10 in each group): control group, model group, short-hairpin RNA (shRNA) control group and short hairpin RNA targeting HOTAIR (shHOTAIR) group. LPS (5 mg/kg) was injected intraperitoneally to establish a rat sepsis model. The expression of HOTAIR and miRNA-138 were detected by real-time reverse-transcriptase PCR (RT-PCR). Hematoxylin-eosin staining was used to observe the pathological changes of liver and lung tissues in rats of each group. The expressions of tumor necrosis factor-alpha (TNF-α), interleukin 6, 4, 10 (IL-6, IL-4, IL-10), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and the phosphorylation of TLR4 and nuclear factor kappa B (NF-kB/p65) were detected using kit assays.

  Results  Compared with those of the control group, the HOTAIR was overexpressed but miRNA-138 was underexpressed in lung tissues of model rats (both P < 0.05); obvious pathological changes were observed in liver and lung tissues of the model rats. Compared with those of the model rats, the pathological changes of the liver and lung tissues of the rats with shHOTAIR treatment were significantly alleviated. Compared with those of the control rats, serum TNF-α, IL-6 and MDA of the model rats increased significantly, while serum IL-4, IL-10, SOD and GSH decreased significantly (P < 0.05 for all); in comparison with those of the model rats, serum TNF-α, IL-6 and MDA of the rats of shHOTAIR group decreased significantly, but serum IL-4, IL-10, SOD and GSH increased significantly (all P < 0.05).

  Conclusion  HOTAIR inhibits inflammatory response and oxidative stress induced by LPS in septic rats by targeting miR-138 and mediating TLR4-dependent signaling pathway.