Uric acid promotes interleukin-17expression to cause kidney injury.

Abstract

Uric acid, an oxidation end-product of purine metabolism, is reportedly to be a risk factor for kidney injury. However, its underlying mechanism is still a mystery. This study aimed to reveal the detailed roles of uric acid in inducing kidney injury and the possible mechanisms. Injection of rats with uric acid significantly increased tubular injury score, and levels of blood urea nitrogen, serum creatinine, and urine kidney injury molecule-1. Uric acid increased the expression of collagen I, alpha-smooth muscle actin, tumor necrosis factor (TNF)-α, interleukin(IL)-1β, and IL-6. Kyoto Encyclopedia of Genes and Genomesanalysis result showed the IL-17 signaling pathway as the most significantly enriched pathway involved in hyperuricemia-related kidney injury. Long-term injection of uric acid induced significant production of IL-17 and recruitment of Th17 cells. Treating rats with the anti-IL-17 mAb attenuated uric acid-induced kidney injury, accompanied by the inactivation of nuclear factor-κB (NF-κB). In conclusion, uric acid was confirmed to be a risk factor for kidney injury via inducing IL-17 expression. Neutralization of IL-17 using the specific mAb relieved uric acid-induced kidney injury via inhibition of NF-κB signaling.