LncRNA-5657 silencing alleviates sepsis-induced lung injury by suppressing the expression of spinster homology protein 2 |
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Institution: | 1. Institute of Physical Science and Information Technology, Anhui University, Hefei 230601, China;2. Department of Respiratory and Critical Care Diseases, 307 Hospital of PLA, Beijing 100071, China;3. Academy of Military Medical Sciences, Beijing 100850, China;4. College of Life Sciences, Jilin University, Changchun 130012, China |
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Abstract: | BackgroundLncRNAs are closely associated with many human major diseases, however, the roles of lncRNAs in sepsis-induced lung injury remain unclear.MethodsHigh-throughput sequencing was used to detect the changes in lncRNA expression profile in alveolar macrophages after LPS stimulation. The BALF of patients with sepsis-induced lung injury was collected. Rats with CLP-induced septic lung injury were treated with sh-lncRNA-5657 via intravenous injection. NR8383 cells were transfected with lentiviral vectors expressing lncRNA-5657, lncRNA-5657 smart silencer, or si-spns2. The BALF cells expression levels of lncRNA-5657 and proinflammatory cytokines in BALF of patients and rats as well as in rat macrophages were measured. Changes in histopathologic score, lung wet/dry weight ratio, and spns2 expression in macrophages were examined. The relationship between lncRNA-5657 and its potential target gene spns2 was validated using a dual-luciferase reporter assay.ResultsThe lncRNA expression profile of LPS-stimulated macrophages demonstrated that lncRNA-5657 showed the greatest fold-change. The BALF cells of patients with sepsis-induced ARDS and the lung tissue of rats with CLP-induced sepsis had significantly increased lncRNA-5657 levels. LncRNA-5657 silencing alleviated CLP-induced lung inflammation in rats. In NR8383 cells, lncRNA-5657 overexpression enhanced, whereas lncRNA-5657 silencing attenuated the expression of proinflammatory cytokines and spns2. A dual-luciferase reporter assay showed that lncRNA-5657 interacted with the promoter of the spns2 gene. Spns2 silencing alleviated LPS-induced inflammatory response and blocked the proinflammatory function of lncRNA-5657 in alveolar macrophages.ConclusionLncRNA-5657 is closely associated with sepsis-induce lung injury. In vitro and in vivo data demonstrated that LncRNA-5657 silencing alleviates sepsis-induced lung injury by inhibiting lung inflammatory response via suppressing spns2 expression. |
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Keywords: | Long noncoding RNA Alveolar macrophages Sepsis Acute respiratory distress syndrome Inflammation |
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