Diabetic nephropathy is one of the most important complications in patients with diabetes. The etiology and pathogenesis of diabetic nephropathy remain unclear. Several studies have indicated that circular RNAs (circRNAs) play crucial regulatory roles in numerous human diseases and normal physiology; however, to date, no study has focused on the comprehensive expression profile of circRNAs in the kidneys of diabetic mice. Therefore, we aimed to identify differentially expressed circRNAs in diabetic mouse kidneys to explore the possible roles of dysregulated circRNAs in diabetic nephropathy development. Diabetic BKS-Leprem2Cd479/Nju (BKS-DB/Nju) mice and their nondiabetic wild-type littermates of C57BL/KsJ wild-type (WT) mice were used as experimental animals. Among all circRNAs identified by high-throughput RNA sequencing, four circRNAs were upregulated and ten were downregulated in diabetic mouse kidneys compared to those in nondiabetic mouse kidneys. After verification using quantitative reverse transcriptase polymerase chain reaction assays, we found that circR_1084, circR_182, circR_4, circR_50, circR_596, circR_897, and circR_203 were downregulated, whereas circR_627, circR_628, circR_735, and circR_801 were upregulated in the renal tissues of 8- and 16-week-old BKS-DB/Nju mice compared to those in WT mice. We studied the circRNA expression profile in the kidneys of diabetic mice. Differentially expressed circRNAs may be useful as candidate biomarkers for diabetic nephropathy. Collectively, our results provide a novel theoretical basis for further investigation of the regulatory roles of circRNA in the etiology and pathogenesis of diabetic nephropathy.

中文翻译：

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转基因糖尿病小鼠肾脏中的环状 RNA 表达谱

糖尿病肾病是糖尿病患者最重要的并发症之一。糖尿病肾病的病因和发病机制尚不清楚。多项研究表明，环状 RNA（circRNA）在多种人类疾病和正常生理机能中起着至关重要的调节作用。然而，迄今为止，还没有研究关注糖尿病小鼠肾脏中 circRNA 的综合表达谱。因此，我们旨在鉴定糖尿病小鼠肾脏中差异表达的 circRNA，以探索失调的 circRNA 在糖尿病肾病发展中的可能作用。糖尿病 BKS-Leprem2Cd479/Nju (BKS-DB/Nju) 小鼠和 C57BL/KsJ 野生型 (WT) 小鼠的非糖尿病野生型同窝小鼠用作实验动物。在通过高通量 RNA 测序鉴定的所有 circRNA 中，与非糖尿病小鼠肾脏相比，糖尿病小鼠肾脏中有 4 个 circRNA 上调，10 个下调。经定量逆转录聚合酶链反应测定验证后，我们发现circR_1084、circR_182、circR_4、circR_50、circR_596、circR_897和circR_203下调，而circR_627、circR_628、circR_80和circR_7在肾组织中下调16 周龄 BKS-DB/Nju 小鼠与 WT 小鼠的比较。我们研究了糖尿病小鼠肾脏中的 circRNA 表达谱。差异表达的 circRNA 可能用作糖尿病肾病的候选生物标志物。总的来说，我们的研究结果为进一步研究 circRNA 在糖尿病肾病病因和发病机制中的调节作用提供了新的理论基础。