Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Department of Animal Biotechnology, National Institute of Genetic Engineering and Biotechnology, P.O. Box: 14965-16, Tehran, Iran.
J Transl Med. 2021 Jul 10;19(1):299. doi: 10.1186/s12967-021-02964-6.
Diabetic nephropathy (DN) has an increasing global prevalence with excessive health expenditure and burden. Exosomal mRNAs regulate intercellular communications and participate in the pathogenesis of various disorders like DN. This study aimed to assess the expression levels of ACE, ELMO1, and WT1 mRNAs in the blood extracellular vesicles (EVs) of DN patients and diabetic patients without nephropathy (DM group) in comparison to healthy controls and investigate their correlations with the severity of DN.
The performed investigation is a cross-sectional study of 256 participants including 103 DN patients, 100 DM patients, and 53 healthy controls. The quantification of WT1, ACE, and ELMO1 mRNAs in the blood EVs were executed using qRT-PCR. The ROC analysis was performed to determine the diagnostic accuracy of mRNAs.
DN patients had significantly higher expressed WT1 mRNA (1.70-fold change) and lower expressed ACE mRNA (0.55-fold change) in the blood EVs compared to DM patients and controls. ELMO1 mRNA was not expressed in EVs of any groups. A positive correlation between WT1 mRNA level and urine Alb/Cr ratio (r = 0.602, p < 0.001) and a negative correlation between ACE mRNA expression and urine Alb/Cr ratio within DN patients (r = - 0.474, p < 0.001) was identified. The accuracy of WT1 mRNA and 1/ACE mRNA for predicting incipient DN was 0.63 (95% CI 0.55, 0.72) and 0.62 (95% CI 0.54, 0.71), and for predicting overt DN was 0.83 (95% CI 0.74, 0.92) and 0.75 (95% CI 0.66, 0.83), respectively.
WT1 and ACE mRNAs level in blood EVs were predictors for early diagnosis of DN therefore their quantifications might be used to determine the severity of albuminuria and glomerular injuries.
糖尿病肾病（DN）的全球患病率不断上升，导致医疗支出和负担过大。外泌体 mRNA 调节细胞间通讯，并参与各种疾病的发病机制，如 DN。本研究旨在评估 DN 患者和无肾病糖尿病（DM 组）患者血液细胞外囊泡（EVs）中 ACE、ELMO1 和 WT1 mRNA 的表达水平，并与健康对照组进行比较，同时研究其与 DN 严重程度的相关性。
本研究为横断面研究，纳入 256 名参与者，包括 103 名 DN 患者、100 名 DM 患者和 53 名健康对照者。采用 qRT-PCR 检测血液 EVs 中 WT1、ACE 和 ELMO1 mRNA 的定量。进行 ROC 分析以确定 mRNAs 的诊断准确性。
与 DM 患者和对照组相比，DN 患者血液 EVs 中 WT1 mRNA 的表达明显升高（1.70 倍变化），ACE mRNA 的表达明显降低（0.55 倍变化）。ELMO1 mRNA 未在任何组的 EVs 中表达。DN 患者的 WT1 mRNA 水平与尿 Alb/Cr 比值呈正相关（r=0.602，p<0.001），ACE mRNA 表达与 DN 患者尿 Alb/Cr 比值呈负相关（r=-0.474，p<0.001）。WT1 mRNA 和 1/ACE mRNA 预测早期 DN 的准确率分别为 0.63（95%CI 0.55,0.72）和 0.62（95%CI 0.54,0.71），预测显性 DN 的准确率分别为 0.83（95%CI 0.74,0.92）和 0.75（95%CI 0.66,0.83）。
血液 EVs 中的 WT1 和 ACE mRNA 水平是 DN 早期诊断的预测因子，因此其定量检测可能用于确定白蛋白尿和肾小球损伤的严重程度。
