Dissanayake Lashodya V, Zietara Adrian, Levchenko Vladislav, Spires Denisha R, Burgos Angulo Mariana, El-Meanawy Ashraf, Geurts Aron M, Dwinell Melinda R, Palygin Oleg, Staruschenko Alexander
Department of Molecular Pharmacology & Physiology, Morsani College of Medicine, University of South Florida, 560 Channelside Dr., Tampa, FL 33602, USA.
Department of Physiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
iScience. 2022 Aug 4;25(9):104887. doi: 10.1016/j.isci.2022.104887. eCollection 2022 Sep 16.
Uric acid (UA) is the final metabolite in purine catabolism in humans. Previous studies have shown that the dysregulation of UA homeostasis is detrimental to cardiovascular and kidney health. The gene encodes for the Xanthine Oxidoreductase enzyme group, responsible for producing UA. To explore how hypouricemia can lead to kidney damage, we created a rat model with the genetic ablation of the gene on the Dahl salt-sensitive rat background (SS). SS rats lacked UA and exhibited impairment in growth and survival. This model showed severe kidney injury with increased interstitial fibrosis, glomerular damage, crystal formation, and an inability to control electrolyte balance. Using a multi-omics approach, we highlighted that lack of leads to increased oxidative stress, renal cell proliferation, and inflammation. Our data reveal that the absence of leads to kidney damage and functional decline by the accumulation of purine metabolites in the kidney and increased oxidative stress.
尿酸（UA）是人体嘌呤分解代谢的终产物。先前的研究表明，尿酸稳态失调对心血管和肾脏健康有害。该基因编码黄嘌呤氧化还原酶基团，负责产生尿酸。为了探究低尿酸血症如何导致肾损伤，我们在 Dahl 盐敏感大鼠背景（SS）上创建了一个基因敲除该基因的大鼠模型。SS 大鼠缺乏尿酸，生长和存活出现障碍。该模型显示出严重的肾损伤，伴有间质纤维化增加、肾小球损伤、晶体形成以及无法控制电解质平衡。通过多组学方法，我们强调缺乏该基因会导致氧化应激增加、肾细胞增殖和炎症。我们的数据表明，缺乏该基因会通过肾脏中嘌呤代谢产物的积累和氧化应激增加导致肾损伤和功能衰退。
