Department of Nephrology, Gongli Hospital of Shanghai Pudong New Area, No. 219 Miaopu Road, Pudong New Area, 200135, Shanghai, China.
BMC Nephrol. 2024 Apr 12;25(1):130. doi: 10.1186/s12882-024-03562-6.
Diabetic nephropathy (DN) manifests a critical aspect in the form of renal tubular injury. The current research aimed to determine the function and mechanism of long non-coding ribonucleic acid (LncRNA) differentiation antagonising non-protein coding RNA (DANCR), with a focus on its impact on renal tubular injury.
Quantitative reverse transcription polymerase chain reaction was employed to analyze the RNA levels of DANCR in the serum of patients with DN or human proximal tubular epithelial cells (human kidney 2 [HK2]). The diagnostic significance of DANCR was assessed using a receiver operating characteristic curve. A DN model was established by inducing HK-2 cells with high glucose (HG). Cell proliferation, apoptosis, and the levels of inflammatory factors, reactive oxygen species (ROS), and malondialdehyde (MDA) were detected using the Cell Counting Kit - 8, flow cytometry, and enzyme-linked immunosorbent assay. The interaction between microRNA (miR)-214-5p and DANCR or Krüppel-like factor 5 (KLF5) was investigated using RNA immunoprecipitation and dual-luciferase reporter assays.
Elevated levels of DANCR were observed in the serum of patients with DN and HG-inducted HK-2 cells (P < 0.05). DANCR levels effectively identified patients with DN from patients with type 2 diabetes mellitus. Silencing of DANCR protected against HG-induced tubular injury by restoring cell proliferation, inhibiting apoptosis, and reducing the secretion of inflammatory factors and oxidative stress production (P < 0.05). DANCR functions as a sponge for miR-214-5p, and the mitigation of DANCR silencing on HG-induced renal tubular injury was partially attenuated with reduced miR-214-5p (P < 0.05). Additionally, KLF5 was identified as the target of miR-214-5p.
DANCR was identified as diagnostic potential for DN and the alleviation of renal tubular injury via the miR-214-5p/KLF5 axis, following DANCR silencing, introduces a novel perspective and approach to mitigating DN.
糖尿病肾病（DN）以肾小管损伤为主要表现。本研究旨在探讨长链非编码 RNA（LncRNA）分化拮抗非编码 RNA（DANCR）的功能和机制，重点研究其对肾小管损伤的影响。
采用定量逆转录聚合酶链反应分析 DN 患者或人近端肾小管上皮细胞（人肾 2 细胞[HK2]）血清中的 DANCR RNA 水平。采用受试者工作特征曲线评估 DANCR 的诊断意义。通过高糖（HG）诱导 HK-2 细胞建立 DN 模型。采用细胞计数试剂盒-8、流式细胞术和酶联免疫吸附试验检测细胞增殖、凋亡及炎症因子、活性氧（ROS）和丙二醛（MDA）水平。采用 RNA 免疫沉淀和双荧光素酶报告基因实验研究微小 RNA（miR）-214-5p 与 DANCR 或 Krüppel 样因子 5（KLF5）的相互作用。
DN 患者血清和 HG 诱导的 HK-2 细胞中 DANCR 水平升高（P<0.05）。DANCR 水平可有效鉴别 DN 患者与 2 型糖尿病患者。沉默 DANCR 可通过恢复细胞增殖、抑制凋亡、减少炎症因子分泌和减轻氧化应激产生来减轻 HG 诱导的肾小管损伤（P<0.05）。DANCR 作为 miR-214-5p 的海绵，沉默 DANCR 减轻 HG 诱导的肾小管损伤的作用部分被 miR-214-5p 减少所减弱（P<0.05）。此外，KLF5 被鉴定为 miR-214-5p 的靶基因。
DANCR 可作为 DN 的潜在诊断标志物，通过沉默 DANCR 减轻 miR-214-5p/KLF5 轴对肾小管损伤的缓解作用，为治疗 DN 提供了新的视角和方法。
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