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

• Published in: Clinical and experimental nephrology Vol. 26; no. 3; pp. 226 - 233
• Main Authors: Onishi, Keisuke, Fu, Hai Ying, Sofue, Tadashi, Tobiume, Atsushi, Moritoki, Masahiro, Saiga, Hiroyuki, Ohmura-Hoshino, Mari, Hoshino, Katsuaki, Minamino, Tetsuo
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.03.2022; Springer Nature B.V
• Subjects: Body temperature; Creatinine; Fluid flow; Galectin-9; Hypothermia; Inflammation; Kidneys; Lipopolysaccharides; Medicine; Medicine & Public Health; Nephrology; Original Article; Permeability; Rodents; Spleen; Tumor necrosis factor-α; Urine; Urology; Galectin-9; Acute kidney injury (AKI); Lipopolysaccharide (LPS); Hypothermia
• ISSN: 1342-1751; 1437-7799
• DOI: 10.1007/s10157-021-02152-2

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.