Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
PLoS One. 2022 Apr 1;17(4):e0265619. doi: 10.1371/journal.pone.0265619. eCollection 2022.
Extracellular vesicles (EVs), including exosomes and microvesicles, are involved in intercellular communication by transferring biomolecules such as mRNA, which has been shown to be as essential biomarkers for many physiological and pathological conditions such as diabetic nephropathy (DN). This study aimed to investigate the expression of CDH1, CDH2, MCP-1, and PAI-1 mRNAs in blood EVs of DN patients and to determine their accuracy in predicting early-stage DN.
We recruited 196 participants, including 35 overt DN patients, 53 incipient DN patients, 62 diabetic patients (DM), and 46 healthy individuals. Quantification of the mRNA profile of blood EVs was performed using the qRT-PCR method. The diagnostic performance of mRNA was evaluated using receiver operating characteristic analysis.
The mRNA expression of CDH2 and MCP-1 was downregulated in overt DN group (0.22-fold change and 0.15-fold change, respectively) and incipient DN group (0.60-fold change and 0.43-fold change, respectively) compared to DM group (1.72-fold change and 2.77-fold change, respectively), while PAI-1 mRNA expression decreased in incipient DN group (0.70-fold change) and DM group (0.58-fold change) compared to control. However, the expression level of CDH1 mRNA was not significantly different among the four groups (p = 0.408). Moreover, CDH2 and MCP-1 mRNAs inversely correlated with creatinine (r = -0.370 and r = -0.361, p<0.001) and Alb/Cr ratio (r = -0.355 and r = -0.297, p<0.001). 1/CDH2 mRNA also predicted overt DN with an accuracy of 0.75 (95%CI: 0.65-0.85) and incipient DN with an accuracy of 0.61 (95%CI: 0.50-0.71) while 1/MCP-1 mRNA had an accuracy of 0.66 (95%CI: 0.55-0.77) for overt DN prediction and an accuracy of 0.61 (95%CI: 0.51-0.71) for incipient DN prediction.
CDH2 and MCP-1 mRNAs expression in blood EVs was decreased with the development of DN, suggesting the renoprotective effect of these mRNAs in diabetic individuals. Moreover, their quantifications could serve as diagnostic biomarkers for early-stage DN.
细胞外囊泡（EVs），包括外泌体和微囊泡，通过转移 mRNA 等生物分子参与细胞间通讯，mRNA 已被证明是许多生理和病理状况（如糖尿病肾病（DN））的重要生物标志物。本研究旨在探讨 DN 患者血液 EVs 中 CDH1、CDH2、MCP-1 和 PAI-1 mRNA 的表达，并确定其在预测早期 DN 中的准确性。
我们招募了 196 名参与者，包括 35 名显性 DN 患者、53 名早期 DN 患者、62 名糖尿病患者（DM）和 46 名健康个体。使用 qRT-PCR 方法定量检测血液 EVs 的 mRNA 谱。使用受试者工作特征分析评估 mRNA 的诊断性能。
与 DM 组相比，显性 DN 组（分别下调 0.22 倍和 0.15 倍）和早期 DN 组（分别下调 0.60 倍和 0.43 倍）中 CDH2 和 MCP-1 的 mRNA 表达降低，而 PAI-1 mRNA 表达在早期 DN 组（下调 0.70 倍）和 DM 组（下调 0.58 倍）中降低。然而，四组间 CDH1 mRNA 的表达水平无显著差异（p = 0.408）。此外，CDH2 和 MCP-1 mRNAs 与肌酐（r = -0.370 和 r = -0.361，p<0.001）和 Alb/Cr 比值（r = -0.355 和 r = -0.297，p<0.001）呈负相关。1/CDH2 mRNA 也可准确预测显性 DN，准确率为 0.75（95%CI：0.65-0.85），预测早期 DN 的准确率为 0.61（95%CI：0.50-0.71），而 1/MCP-1 mRNA 预测显性 DN 的准确率为 0.66（95%CI：0.55-0.77），预测早期 DN 的准确率为 0.61（95%CI：0.51-0.71）。
DN 发展过程中血液 EVs 中 CDH2 和 MCP-1 mRNA 的表达降低，提示这些 mRNA 在糖尿病个体中具有肾保护作用。此外，它们的定量可以作为早期 DN 的诊断生物标志物。
