Kidney and plasma metabolomics provide insights into the molecular mechanisms of urate nephropathy in a mouse model of hyperuricemia
Kidney and plasma metabolomics provide insights into the molecular mechanisms of urate nephropathy in a mouse model of hyperuricemia
复制标题
肾脏和血浆代谢组学为高尿酸血症小鼠模型中尿酸盐肾病的分子机制提供了见解
DOI：
10.1016/j.bbadis.2022.166374
复制
发表时间：
2022-03-14
影响因子：
6.2
通讯作者：
Li，Changgui
中科院分区：
文献类型：
--
作者：
Li，Hailong;Zhang，Hui;Li，Changgui
高尿酸血症(HUA)与人类肾脏损害和肾脏疾病密切相关，然而，HUA引起肾脏疾病的潜在机制尚不清楚。在本研究中，我们检测了通过敲除(Ko)尿酸氧化酶(Uox)基因构建的HUA小鼠模型的肾脏和血浆代谢特征。UOX-KO小鼠尿酸、甘氨酸、3‘-腺苷一磷酸、柠檬酸、N-乙酰-L-谷氨酸、L-犬尿氨酸、5-羟基吲哚乙酸酯、黄原酸、皮质醇和(−)-前列腺素E_2升高，肾脏肌苷减少。这些改变的代谢产物证实了Uox-Ko小鼠的嘌呤代谢、氨基酸生物合成、色氨酸代谢和神经活性配体-受体相互作用的障碍。甜菜碱和生物素与肾脏功能有关，是预测尿酸肾病(UN)的潜在血浆代谢生物标志物。综上所述，这些结果揭示了UN的潜在致病机制。研究这些途径可能会为联合国的治疗干预提供新的靶点，并可能导致新的治疗策略。
Hyperuricemia (HUA) is closely associated with kidney damage and kidney diseases in humans; however, the underlying mechanisms of HUA-induced kidney diseases remain unknown. In the present study, we examined the kidney and plasma metabolic profiles in a HUA mouse model constructed by knocking out (Ko) the urate oxidase (Uox) gene. The Uox-Ko mice were characterized by an increase in uric acid, glycine, 3′-adenosine monophosphate, citrate,N-acetyl-l-glutamate,l-kynurenine, 5-hydroxyindoleacetate, xanthurenic acid, cortisol, and (−)-prostaglandin e2 together with a decrease of inosine in the kidneys. These altered metabolites confirmed disturbances of purine metabolism, amino acid biosynthesis, tryptophan metabolism, and neuroactive ligand-receptor interaction in Uox-Ko mice. Betaine and biotin were related to kidney function and identified as the potential plasma metabolic biomarker for predicting urate nephropathy (UN). Taken together, these results revealed the underlying pathogenic mechanisms of UN. Investigating these pathways might provide novel targets for the therapeutic intervention of UN and can potentially lead to new treatment strategies.