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Galectin-9 deficiency exacerbates lipopolysaccharide-induced hypothermia and kidney injury

Abstract

Background

Galectin-9 (Gal-9) is a multifunctional lectin that moderates inflammation and organ damage. In this study, we tested whether Gal-9 has a protective role in the pathogenesis of endotoxemic acute kidney injury.

Methods

We examined the levels of Gal-9 in control mice after lipopolysaccharide (LPS) administration. We developed Gal-9 knockout (KO) mice that lack Gal-9 systemically and evaluated the role of Gal-9 in LPS-induced proinflammatory cytokines, vascular permeability, and renal injury.

Results

Gal-9 levels were increased in the plasma, kidney, and spleen within 4 h after LPS administration to wild-type mice. Gal-9 deficiency did not affect the LPS-induced increase in plasma tumor necrosis factor-α levels at 1 h or vascular permeability at 6 h. Lower urine volume and reduced creatinine clearance were observed in Gal-9-KO mice compared with wild-type mice after LPS administration. Gal-9-KO mice had limited improvement in urine volume after fluid resuscitation compared with wild-type mice. LPS reduced the body temperature 12 h after its administration. Hypothermia had disappeared in wild-type mice by 24 h, whereas it was sustained until 24 h in Gal-9-KO mice. Importantly, maintaining body temperature in Gal-9-KO mice improved the response of urine flow to fluid resuscitation.

Conclusion

Deficiency in Gal-9 worsened LPS-induced hypothermia and kidney injury in mice. The accelerated hypothermia induced by Gal-9 deficiency contributed to the blunted response to fluid resuscitation.

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Acknowledgements

We thank Yoshihide Fujisawa, Ph.D., from the Life Science Research Center, Kagawa University (Kagawa, Japan) and Yoshiko Watanabe, B.S., from the Department of Cardiorenal and Cerebrovascular Medicine, Faculty of Medicine, Kagawa University (Kagawa, Japan) for technical assistance and for help in maintaining the mouse colony. We thank J. Ludovic Croxford, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.

Funding

This work was supported in part by a 2021 grant from the Kagawa University Research Promotion Program (to KO), and a JSPS KAKENHI grant (no. 24590466 to MH).

Author information

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Authors

Contributions

KO contributed to the study conception and design. Material preparation, data collection, and analysis were performed by KO and then HS, KH, and MH developed the transgenic mouse line. The first draft of the manuscript was written by KO and then TS and HF commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Keisuke Onishi.

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Conflict of interest

The authors have declared that no conflict of interest exists.

Ethical approval

This study was approved by the Institutional Animal Care and Use Committee of Kagawa University (#20616) and followed standard guidelines for the humane care and use of animals in scientific research.

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Onishi, K., Fu, H.Y., Sofue, T. et al. Galectin-9 deficiency exacerbates lipopolysaccharide-induced hypothermia and kidney injury. Clin Exp Nephrol (2021). https://doi.org/10.1007/s10157-021-02152-2

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Keywords

  • Lipopolysaccharide (LPS)
  • Acute kidney injury (AKI)
  • Galectin-9
  • Hypothermia