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Kidney Week

Abstract: PO0200

Lipopolysaccharide Induces NEAT 1 Expression in AKI via TLR4/NF-κB Signaling

Session Information

  • AKI Mechanisms - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Xue, Rui, University of Hong Kong, Hong Kong, Hong Kong
  • Yiu, Wai Han, University of Hong Kong, Hong Kong, Hong Kong
  • Lok, Sarah W.Y., University of Hong Kong, Hong Kong, Hong Kong
  • Chan, Loretta Y.Y., University of Hong Kong, Hong Kong, Hong Kong
  • Leung, Joseph C K, University of Hong Kong, Hong Kong, Hong Kong
  • Lai, Kar Neng, University of Hong Kong, Hong Kong, Hong Kong
  • Lan, Hui Y., The Chinese University of Hong Kong, Hong Kong, Hong Kong
  • Tang, Sydney C.W., University of Hong Kong, Hong Kong, Hong Kong
Background

Toll-like receptor 4 (TLR4)/ Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) have been implicated in the pathogenesis of acute kidney injury(AKI). Nuclear Paraspeckle Assembly Transcript 1 (NEAT1) is a long non-coding RNA that plays key roles in a variety of biological processes and is involved in many other diseases. Beyond its fundamental role of maintaining function of the nucleus, it remains unknown whether interaction between TLR4/NF-κB signaling and NEAT1 is involved in the process of the development of AKI.

Methods

Septic AKI model was established with injection of LPS into mice. Mouse tubular cells were stimulated with LPS for the study of tubular inflammation. The role and upstream regulatory mechanisms of NEAT1 in the inflammatory processes were studied by using signaling inhibitors.

Results

In LPS-induced AKI, NEAT1 expression was upregulated in tubular cells, accompanied by elevated TLR4/NF-κB signaling In vitro, mouse tubular cells treated with LPS also showed increase in NEAT1, prior to the production of proinflammatory cytokines including IL-6 and CCL-2, whereas treatment with an inhibitor of TLR4 or NF-κB signaling suppressed LPS-induced NEAT1 expression.

Conclusion

NEAT1 expression was induced in LPS-induced AKI model via TLR4/NF-κB signaling, suggesting its potential role in the inflammatory process. Our findings open the door to exploit NEAT1 expression as a potential novel therapeutic approach for AKI and other inflammation-related renal diseases.

Funding: Research Grants Council of Hong Kong (Collaborative Research Fund, grant no. C7018-16G), and Hong Kong Society of Nephrology/HK Kidney Foundation Research Grant 2019.