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LncRNA PVT1 accelerates LPS-induced septic acute kidney injury through targeting miR-17-5p and regulating NF-κB pathway

  • Nephrology - Original Paper
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Abstract

Background

Long noncoding RNA PVT1 is associated with diverse human diseases, including acute kidney injury (AKI). However, our understandings of PVT1 on septic AKI are limited.

Methods

The septic AKI model was constructed through lipopolysaccharide (LPS) treatment. PVT1 and miR-17-5p levels were measured using qRT-PCR analysis. The concentrations of inflammatory cytokines were determined with ELISA kits. Cell viability and apoptosis were assessed using CCK-8 assay and flow-cytometric analysis, respectively. Protein levels were examined using western blot assay. The targeting association between miR-17-5p and PVT1 was verified by dual-luciferase reporter, RIP and RNA pull-down assays.

Results

PVT1 level was elevated and miR-17-5p level was declined in septic AKI patients’ serum and LPS-stimulated HK-2 cells. Cell viability was suppressed and cell apoptosis and inflammation were promoted after LPS treatment. PVT1 knockdown or miR-17-5p elevation restored LPS-mediated HK-2 cell injury. MiR-17-5p was sponged by PVT1, and its inhibition weakened the impact of PVT1 deficiency on LPS-mediated injury of HK-2 cells. In addition, PVT1 knockdown inactivated NF-κB pathway mediated by LPS treatment, but miR-17-5p inhibition further reversed this effect.

Conclusion

PVT1 knockdown promoted cell viability, suppressed inflammatory response and apoptosis by regulating miR-17-5p expression and NF-κB pathway in LPS-stimulated HK-2 cells.

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Funding

This work was supported by Jingzhou Science and Technology Bureau Project: Study on the relationship between polymorphism of endotoxin receptor TLR4 gene and susceptibility to sepsis in Jingzhou area (D2018014).

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Author notes

  1. Wensheng Yuan and Xiaoqing Xiong contributed equally to this work.

Authors and Affiliations

  1. Emergency Department, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, No. 1 Renmin Road, Jingzhou, 433000, Hubei, China

    Wensheng Yuan & Xiaoqing Xiong

  2. ICU Department, Jingzhou Central Hospital, The Second Clinical Medical College, Yangtze University, Jingzhou, Hubei, China

    Jinlong Du, Qi Fan, Rong Wang & Xia Zhang

Authors
  1. Wensheng Yuan
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  2. Xiaoqing Xiong
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  6. Xia Zhang
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Correspondence to Wensheng Yuan.

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Yuan, W., Xiong, X., Du, J. et al. LncRNA PVT1 accelerates LPS-induced septic acute kidney injury through targeting miR-17-5p and regulating NF-κB pathway. Int Urol Nephrol 53, 2409–2419 (2021). https://doi.org/10.1007/s11255-021-02905-8

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  • DOI: https://doi.org/10.1007/s11255-021-02905-8

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