Influence of lncRNA MALAT1 on septic lung injury in mice through p38 MAPK/p65 NF-κB pathway

OBJECTIVE: To investigate the influence of long non-coding ribonucleic acid (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on septic lung injury in mice and its mechanism, so as to provide references for the clinical prevention and treatment of septic lung injury in the future.

MATERIALS AND METHODS: A total of 60 male C57 mice were randomly divided into Control group (n=20), lipopolysaccharide (LPS) group (n=20), and LPS+MALAT1 siRNA group (n=20) using a random number table. The mouse model of septic lung injury was established via intraperitoneal injection of LPS (10 mg/kg), and the MALAT1 knockdown model was established via tail intravenous injection of MALAT1 siRNA. After 12 h, the lung was taken to measure the wet weight/dry weight ratio. Also, the activity of myeloperoxidase (MPO) in lung tissues was detected. The number of neutrophils and macrophages in bronchoalveolar lavage fluid (BALF) was detected via bronchoalveolar lavage. Moreover, the messenger RNA (mRNA) expression levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and IL-6, in lung tissues were detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Finally, the expression level of p38 in lung tissues was detected via immunohistochemical staining, and the expressions of p38 mitogen-activated protein kinase (MAPK)/p65 nuclear factor-κB (NF-κB) signaling pathway-related proteins in lung tissues of mice were detected via Western blotting.

RESULTS: The expression of lncRNA MALAT1 in lung tissues of mice with septic lung injury was significantly increased (p<0.05). After knockdown of lncRNA MALAT1, the LPS-induced pathological injury of lungs could be improved, and the wet weight/dry weight ratio of lungs could be reduced (p<0.05). Compared with those in LPS group, the total number of inflammatory cells and the number of neutrophils and macrophages in BALF were significantly decreased in LPS+MALAT1 siRNA group (p<0.05), and the levels of inflammatory cytokines were also significantly inhibited (p<0.05). The immunohistochemical results manifested that the knockdown of lncRNA MALAT1 could inhibit the LPS-induced up-regulation of p38 in lung tissues in mice. According to the results of Western blotting, the p38 MAPK/p65 NF-κB signaling pathway was significantly activated in lung tissues in LPS group (p<0.05), while it was significantly suppressed after inhibition on lncRNA MALAT1 (p<0.05).

CONCLUSIONS: The knockdown of lncRNA MALAT1 can significantly improve the septic lung injury in mice, whose mechanism may be related to its inhibition on the p38 MAPK/p65 NF-κB signaling pathway.

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