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LncRNA NEAT1 Knockdown Alleviates Lipopolysaccharide-Induced Acute Lung Injury by Modulation of miR-182-5p/WISP1 Axis

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Abstract

Accumulating evidence has demonstrated the vital roles of long non-coding RNAs (lncRNAs) in acute lung injury (ALI). In this study, we aimed to explore the effect of Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) on ALI development. The ALI mice and cell models were constructed using lipopolysaccharide (LPS)-induced method. The concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) were measured by enzyme-linked immunosorbent assay (ELISA). The levels of TNF-α mRNA, IL-6 mRNA, IL-1β mRNA, NEAT1, miR-182-5p, and WNT-inducible secreted protein 1 (WISP1) mRNA were determined by quantitative real-time polymerase chain reaction (qRT-PCR) assay. Cell viability was evaluated by Cell Counting Kit-8 (CCK-8) assay. The level of lactate dehydrogenase (LDH) and the activity of caspase-3 were measured by specific kits. The interaction between miR-182-5p and NEAT1 or WISP1 was investigated by dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. Protein levels were measured by Western blot assay. NEAT1 level was elevated in LPS-induced ALI mice and LPS-stimulated MH-S cells. LPS treatment repressed MH-S cell viability and promoted apoptosis and inflammation, while NEAT1 silencing restored the impacts. For mechanism analysis, NEAT1 was identified as the sponge for miR-182-5p to positively regulate WISP1 expression. Moreover, NEAT1 knockdown could accelerate cell viability and inhibit cell apoptosis and inflammation in LPS-induced MH-S cells by elevating miR-182-5p and decreasing WISP1 in LPS-exposed MH-S cells. In addition, NEAT1 deficiency blocked the activation of NF-κB pathway caused by LPS in MH-S cells. NEAT1 overexpression restrained cell viability and facilitated cell apoptosis and inflammation in LPS-exposed MH-S cells through miR-182-5p/WISP1 axis.

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Authors and Affiliations

  1. Department of Respiratory and Critical Care Medicine, Qingdao Municipal Hospital (Headquarters), No.1 Jiaozhou Road, Shibei District, Qingdao, 266011, Shandong, China

    Sensen Lv & Yun Wang

  2. Department of Critical Care Medicine, Qingdao Municipal Hospital (East Brach), No.5 Donghai Middle Road, Shinan District, Qingdao, 266071, Shandong, China

    Xiaolu Qu & Yan Qu

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  1. Sensen Lv
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  2. Xiaolu Qu
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  3. Yan Qu
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  4. Yun Wang
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Contributions

YQ designed and supervised the study. SL conducted the experiments and drafted the manuscript. YW collected and analyzed the data. XQ contributed the methodology and edited the manuscript. All the authors read and approved the final manuscript.

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Correspondence to Yan Qu or Yun Wang.

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The authors declare that they have no conflict of interest.

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The animal experiments were allowed by the Ethics Committee of Animal Research of Qingdao Municipal Hospital.

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Lv, S., Qu, X., Qu, Y. et al. LncRNA NEAT1 Knockdown Alleviates Lipopolysaccharide-Induced Acute Lung Injury by Modulation of miR-182-5p/WISP1 Axis. Biochem Genet 59, 1631–1647 (2021). https://doi.org/10.1007/s10528-021-10081-8

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  • DOI: https://doi.org/10.1007/s10528-021-10081-8

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