Department of Nephrology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou 570311, China.
Department of Neurosurgery, First Affiliated Hospital of Hainan Medical University, Haikou 570100, China.
Acta Biochim Biophys Sin (Shanghai). 2022 Sep 25;54(9):1365-1375. doi: 10.3724/abbs.2022128.
Renal fibrosis is most common among chronic kidney diseases. Molecular studies have shown that long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) participate in renal fibrosis, while the roles of lncRNA taurine upregulated gene 1 (TUG1) and miR-140-3p in hyperuricemia-induced renal fibrosis remain less investigated. In this study, a rat hyperuricemia model is constructed by oral administration of adenine. TUG1, miR-140-3p, and cathepsin D (CtsD) expression levels in rat models are measured. After altering TUG1, miR-140-3p, or CtsD expression in modelled rats, biochemical indices, including uric acid (UA), serum creatine (SCr), blood urea nitrogen (BUN), and 24-h urine protein are detected, pathological changes in the renal tissues, and renal fibrosis are examined. In renal tissues from hyperuricemic rats, TUG1 and CtsD are upregulated, while miR-140-3p is downregulated. Inhibiting TUG1 or CtsD or upregulating miR-140-3p relieves renal fibrosis in hyperuricemic rats. Downregulated miR-140-3p reverses the therapeutic effect of TUG1 reduction, while overexpression of CtsD abolishes the role of miR-140-3p upregulation in renal fibrosis. Collectively, this study highlights that TUG1 inhibition upregulates miR-140-3p to ameliorate renal fibrosis in hyperuricemic rats by inhibiting CtsD.
肾纤维化是慢性肾脏病中最常见的。分子研究表明，长链非编码 RNA（lncRNA）和 microRNA（miRNA）参与肾纤维化，而 lncRNA 牛磺酸上调基因 1（TUG1）和 miR-140-3p 在高尿酸血症诱导的肾纤维化中的作用研究较少。本研究通过给予腺嘌呤口服构建大鼠高尿酸血症模型。测定大鼠模型中 TUG1、miR-140-3p 和组织蛋白酶 D（CtsD）的表达水平。在改变模型大鼠中的 TUG1、miR-140-3p 或 CtsD 的表达后，检测生化指标，包括尿酸（UA）、血清肌酐（SCr）、血尿素氮（BUN）和 24 小时尿蛋白，观察肾脏组织的病理变化和肾纤维化。在高尿酸血症大鼠的肾组织中，TUG1 和 CtsD 上调，而 miR-140-3p 下调。抑制 TUG1 或 CtsD 或上调 miR-140-3p 可减轻高尿酸血症大鼠的肾纤维化。下调的 miR-140-3p 逆转了 TUG1 减少的治疗效果，而过表达的 CtsD 则消除了 miR-140-3p 上调在肾纤维化中的作用。综上所述，该研究强调了 TUG1 抑制通过抑制 CtsD 上调 miR-140-3p 来改善高尿酸血症大鼠的肾纤维化。
