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

Clin Exp Nephrol. 2022 Mar;26(3):226-233. doi: 10.1007/s10157-021-02152-2. Epub 2021 Oct 26.


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.

Keywords: Acute kidney injury (AKI); Galectin-9; Hypothermia; Lipopolysaccharide (LPS).

MeSH terms

  • Acute Kidney Injury* / chemically induced
  • Acute Kidney Injury* / pathology
  • Animals
  • Galectins / adverse effects
  • Galectins / genetics
  • Humans
  • Hypothermia, Induced*
  • Kidney / pathology
  • Lipopolysaccharides
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout


  • Galectins
  • Lipopolysaccharides