Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Malaysia.
Kidney Blood Press Res. 2022;47(2):81-93. doi: 10.1159/000518866. Epub 2022 Jan 11.
Diabetic kidney disease (DKD) remains the leading cause of chronic kidney disease. Dysregulation of circulating miRNAs has been reported, suggesting their pathological roles in DKD. This study aimed to investigate differentially expressed miRNAs in the sera of type 2 diabetes mellitus (T2DM) patients with and without albuminuria in a selected Malaysian population.
Forty-one T2DM patients on follow-up at a community clinic were divided into normo-(NA), micro-(MIC), and macroalbuminuria (MAC) groups. Differential levels of miRNAs in 12 samples were determined using the pathway-focused (human fibrosis) miScript miRNA qPCR array and was validated in 33 samples, using the miScript custom qPCR array (CMIHS02742) (Qiagen GmbH, Hilden, Germany).
Trends of upregulation of 3 miRNAs in the serum, namely, miR-874-3p, miR-101-3p, and miR-145-5p of T2DM patients with MAC compared to those with NA. Statistically significant upregulation of miR-874-3p (p = 0.04) and miR-101-3p (p = 0.01) was seen in validation cohort. Significant negative correlations between the estimated glomerular filtration rate (eGFR) and miR-874-3p (p = 0.05), miR-101-3p (p = 0.03), and miR-145-5p (p = 0.05) as well as positive correlation between miR-874-3p and age (p = 0.03) were shown by Pearson's correlation coefficient analysis.
Upregulation of previously known miRNA, namely, miR-145-5p, and possibly novel ones, namely, miR-874-3p and miR-101-3p in the serum of T2DM patients, was found in this study. There was a significant correlation between the eGFR and these miRNAs. The findings of this study have provided encouraging evidence to further investigate the putative roles of these differentially expressed miRNAs in DKD.
糖尿病肾病（DKD）仍然是慢性肾脏病的主要原因。有报道称循环 miRNA 失调，提示它们在 DKD 中的病理作用。本研究旨在调查在选定的马来西亚人群中，2 型糖尿病（T2DM）患者伴或不伴白蛋白尿的血清中差异表达的 miRNA。
41 名在社区诊所接受随访的 T2DM 患者分为正常白蛋白尿（NA）、微量白蛋白尿（MIC）和大量白蛋白尿（MAC）组。使用靶向通路（人类纤维化）miScript miRNA qPCR 阵列测定 12 个样本中的差异 miRNA 水平，并使用 miScript 定制 qPCR 阵列（CMIHS02742）（Qiagen GmbH，德国希尔德斯海姆）在 33 个样本中进行验证。
与 NA 相比，MAC 的 T2DM 患者血清中 miR-874-3p、miR-101-3p 和 miR-145-5p 等 3 种 miRNA 的上调趋势。miR-874-3p（p=0.04）和 miR-101-3p（p=0.01）在验证队列中均有统计学意义的上调。Pearson 相关系数分析显示，miR-874-3p、miR-101-3p 和 miR-145-5p 与估算肾小球滤过率（eGFR）呈显著负相关（p=0.05、p=0.03 和 p=0.05），miR-874-3p 与年龄呈显著正相关（p=0.03）。
本研究发现，T2DM 患者血清中先前已知的 miRNA（miR-145-5p）和可能是新的 miRNA（miR-874-3p 和 miR-101-3p）上调。eGFR 与这些 miRNA 之间存在显著相关性。本研究的结果为进一步研究这些差异表达的 miRNA 在 DKD 中的潜在作用提供了令人鼓舞的证据。
