This study was designed to evaluate the diagnostic value of miR-483–5p in diabetic nephropathy (DN), and its effect and mechanism on apoptosis and inflammation of human proximal renal tubular cells (HK2) induced by high glucose (HG). Thirty healthy controls, 30 types 2 diabetes mellitus (T2DM) patients, and 28 DN patients were enrolled. miR-483–5p mRNA levels in serum were analyzed by RT-qPCR assays. The receiver operating characteristic curve (ROC) was used to analyze the diagnostic value of miR-483–5p in DN. HK2 cells were induced by HG to establish an in vitro study model. CCK-8 and flow cytometry was used to detect cell viability, apoptosis, and reactive oxygen species (ROS) generation. Inflammation levels were measured by ELISA. Luciferase reporter assay was used to detect target genes of miR-483–5p. miR-483–5p was decreased in DN patients. The decreased level of miR-483–5p was positively correlated with estimated glomerular filtration rate (eGFR) and negatively correlated with proteinuria. miR-483–5p can significantly distinguish DN patients from healthy controls and T2DM and has a high diagnostic value. miR-483–5p decreased in HK2 cells induced by HG, and overexpression of miR-483–5p reversed HG-induced decreased cell activity, increased apoptosis, ROS production, and inflammation. Histone deacetylase 4 (HDCA4) was markedly increased in DN patients and HG-induced HK2 cells. miR-483–5p directly targeted HDCA4, and increasing miR-483–5p inhibited HDCA4 increased in HG-induced HK2. In conclusion, the results indicate that reduction of miR-483–5p has a high diagnostic value in DN, and overexpression of miR-483–5p has a certain protective effect on HK2 cells induced by HG by targeting HDCA4.

中文翻译：

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miRNA-483–5p 靶向 HDCA4 调节糖尿病肾病中的肾小管损伤

本研究旨在评估miR-483-5p在糖尿病肾病（DN）中的诊断价值，及其对高糖（HG）诱导的人近端肾小管细胞（HK2）凋亡和炎症的影响和机制。招募了 30 名健康对照、30 名 2 型糖尿病 (T2DM) 患者和 28 名 DN 患者。通过RT-qPCR测定分析血清中的miR-483-5p mRNA水平。采用受试者工作特征曲线（ROC）分析miR-483-5p对DN的诊断价值。HG诱导HK2细胞建立体外研究模型。CCK-8 和流式细胞术用于检测细胞活力、细胞凋亡和活性氧 (ROS) 生成。通过ELISA测量炎症水平。荧光素酶报告基因检测用于检测 miR-483-5p 的靶基因。DN 患者中 miR-483-5p 降低。miR-483-5p 水平的降低与估计的肾小球滤过率 (eGFR) 呈正相关，与蛋白尿呈负相关。miR-483-5p可显着区分DN患者与健康对照和T2DM，具有较高的诊断价值。HG 诱导的 HK2 细胞中 miR-483-5p 降低，而 miR-483-5p 的过表达逆转了 HG 诱导的细胞活性降低、细胞凋亡增加、ROS 产生和炎症。组蛋白去乙酰化酶 4 (HDCA4) 在 DN 患者和 HG 诱导的 HK2 细胞中显着增加。miR-483-5p 直接靶向 HDCA4，增加 miR-483-5p 抑制 HDCA4 在 HG 诱导的 HK2 中增加。总之，结果表明 miR-483-5p 的减少在 DN 中具有很高的诊断价值，