Circular RNA (circRNA) is key regulator of diabetic nephropathy (DN) progression. However, the role of circ_0008529 in DN progression remains to be better deciphered. Cell viability, cell cycle, apoptosis and inflammation were measured by MTS assay, flow cytometry and corresponding assay kits. RT-qPCR was used to assess the expression of circ_0008529, miR-185-5p and SMAD family member 2 (SMAD2). Also, western blotting was performed to measure protein expression. Target relationship was validated by RNA pull-down assay, dual-luciferase reporter assay and RNA immunoprecipitation assay. Urinary exosome was isolated using ultracentrifugation method and identified by transmission electron microscopy. Receiver operating characteristic curve was used to analyze the diagnostic value of circ_0008529 in DN patients. Circ_0008529 and SMAD2 were upregulated, while miR-185-5p was downregulated in high glucose (HG)-induced renal tubular HK-2 cells. Under HG treatment, cell viability and cell cycle process were suppressed, while apoptosis, inflammation and extracellular matrix accumulation were enhanced. However, interfering circ_0008529 could attenuate HG-induced effects, and this protection was abated by miR-185 inhibition or SMAD2 re-expression. Mechanically, circ_0008529 and SMAD2 were competing endogenous RNAs for miR-185-5p via target binding, and circ_0008529 regulated SMAD2 expression via miR-185-5p. Notably, circ_0008529 expression was upregulated in urinary exosomes of DN patients, and showed diagnostic value (Sensitivity: 70.21%; Specificity: 86.67%). Circ_0008529 might be a potential target for DN, which regulated DN progression via miR-185-5p/SMAD2 pathway.

环状 RNA (circRNA) 是糖尿病肾病 (DN) 进展的关键调节因子。然而，circ_0008529 在 DN 进展中的作用仍有待更好地解读。通过MTS测定、流式细胞仪和相应的测定试剂盒测量细胞活力、细胞周期、细胞凋亡和炎症。RT-qPCR 用于评估 circ_0008529、miR-185-5p 和 SMAD 家族成员 2 (SMAD2) 的表达。此外，还进行蛋白质印迹来测量蛋白质表达。通过 RNA Pull-down 测定、双荧光素酶报告基因测定和 RNA 免疫沉淀测定验证靶标关系。采用超速离心法分离尿液外泌体，并通过透射电子显微镜进行鉴定。采用受试者工作特征曲线分析circ_0008529对DN患者的诊断价值。Circ_0008529 和 SMAD2 上调，而miR-185-5p在高糖（HG）诱导的肾小管HK-2细胞中下调。在HG处理下，细胞活力和细胞周期过程受到抑制，而细胞凋亡、炎症和细胞外基质积累则增强。然而，干扰 circ_0008529 可以减弱 HG 诱导的作用，并且这种保护作用可以通过抑制 miR-185 或 SMAD2 重新表达而减弱。从机制上讲，circ_0008529和SMAD2是通过靶标结合竞争miR-185-5p的内源RNA，并且circ_0008529通过miR-185-5p调节SMAD2表达。值得注意的是，circ_0008529在DN患者尿液外泌体中表达上调，并显示出诊断价值（敏感性：70.21％；特异性：86.67％）。Circ_0008529可能是DN的潜在靶点，它通过miR-185-5p/SMAD2途径调节DN进展。