Asymptomatic Hyperuricemia Promotes Recovery from Ischemic Organ Injury by Modulating the Phenotype of Macrophages

Gnemmi, Viviane; Li, Qiubo; Ma, Qiuyue; De Chiara, Letizia; Carangelo, Giulia; Li, Chenyu; Molina-Van den Bosch, Mireia; Romagnani, Paola; Anders, Hans-Joachim und Steiger, Stefanie (2022): Asymptomatic Hyperuricemia Promotes Recovery from Ischemic Organ Injury by Modulating the Phenotype of Macrophages. In: Cells, Bd. 11, Nr. 4, 626

Abstract

Acute organ injury, such as acute kidney injury (AKI) and disease (AKD), are major causes of morbidity and mortality worldwide. Hyperuricemia (HU) is common in patients with impaired kidney function but the impact of asymptomatic HU on the different phases of AKI/AKD is incompletely understood. We hypothesized that asymptomatic HU would attenuate AKD because soluble, in contrast to crystalline, uric acid (sUA) can attenuate sterile inflammation. In vitro, 10 mg/dL sUA decreased reactive oxygen species and interleukin-6 production in macrophages, while enhancing fatty acid oxidation as compared with a physiological concentration of 5 mg/dL sUA or medium. In transgenic mice, asymptomatic HU of 7-10 mg/dL did not affect post-ischemic AKI/AKD but accelerated the recovery of kidney excretory function on day 14. Improved functional outcome was associated with better tubular integrity, less peritubular inflammation, and interstitial fibrosis. Mechanistic studies suggested that HU shifted macrophage polarization towards an anti-inflammatory M2-like phenotype characterized by expression of anti-oxidative and metabolic genes as compared with post-ischemic AKI-chronic kidney disease transition in mice without HU. Our data imply that asymptomatic HU acts as anti-oxidant on macrophages and tubular epithelial cells, which endorses the recovery of kidney function and structure upon AKI.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• Sprache: Englisch