Wu Qinghua, Qin Yanan, Shi Mei, Yan Liping
Department of Nephrology, Dongying People's Hospital, Dongying, Shandong, China.
Department of Obstetrics, Dongying People's Hospital, Dongying, Shandong, China.
J Chin Med Assoc. 2021 May 1;84(5):491-497. doi: 10.1097/JCMA.0000000000000522.
Lupus nephritis (LN) is one of the main risk factors contributing to morbidity and mortality of systemic lupus erythematosus (SLE). This study aimed to investigate the potential role of miR-485-5p in human LN.
Quantitative real-time polymerase chain reaction was used for the measurement of miR-485-5p levels. The levels of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in serum were determined by enzyme-linked immunosorbent assay. The diagnostic role of miR-485-5p in LN was evaluated by the receiver operating characteristic (ROC) curve. The impact of miR-485-5p on end-stage renal disease (ESRD) was compared by Kaplan-Meier analysis and Cox regression analysis. The target gene was determined by a dual-luciferase reporter assay system.
MiR-485-5p was highly expressed in SLE and LN patients compared with the healthy controls, and LN patients had the highest level of miR-485-5p. The expression level of miR-485-5p in active LN patients was significantly increased compared with that in nonactive cases. MiR-485-5p expression showed a positive correlation with the levels of estimated glomerular filtration rate, serum creatinine, proteinuria, SLE disease activity index score, and inflammatory cytokines. The ROC analysis results indicated that serum miR-485-5p was a promising biomarker for the early diagnosis of LN, and it can distinguish active LN patients from nonactive ones. Phosphatase and tensin homolog was a direct target of miR-485-5p, and negatively associated with serum miR-485-5p levels. More ESRD events were observed in cases with high miR-485-5p expression, miR-485-5p was an independent factor for the risk of ESRD in LN patients.
Serum miR-485-5p might be a novel promising diagnostic marker for LN and has potential predictive value for ESRD risk in LN patients.
狼疮性肾炎(LN)是导致系统性红斑狼疮(SLE)发病和死亡的主要危险因素之一。本研究旨在探讨miR-485-5p在人类LN中的潜在作用。
采用定量实时聚合酶链反应检测miR-485-5p水平。通过酶联免疫吸附测定法测定血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)的水平。通过受试者操作特征(ROC)曲线评估miR-485-5p在LN中的诊断作用。通过Kaplan-Meier分析和Cox回归分析比较miR-485-5p对终末期肾病(ESRD)的影响。通过双荧光素酶报告基因检测系统确定靶基因。
与健康对照相比,miR-485-5p在SLE和LN患者中高表达,且LN患者的miR-485-5p水平最高。与非活动期LN患者相比,活动期LN患者中miR-485-5p的表达水平显著升高。miR-485-5p表达与估计肾小球滤过率、血清肌酐、蛋白尿、SLE疾病活动指数评分和炎性细胞因子水平呈正相关。ROC分析结果表明,血清miR-485-5p是LN早期诊断的一个有前景的生物标志物,并且可以区分活动期LN患者和非活动期患者。磷酸酶和张力蛋白同源物是miR-485-5p的直接靶标,且与血清miR-485-5p水平呈负相关。在miR-485-5p高表达的病例中观察到更多的ESRD事件,miR-485-5p是LN患者发生ESRD风险的独立因素。
血清miR-485-5p可能是LN一种新型且有前景的诊断标志物,对LN患者的ESRD风险具有潜在预测价值。