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新的糖尿病肾病风险因素:miRNA-196-3p 和 miRNA-203。

New risk factors in diabetic nephropathy: microRNA-196-3p and microRNA-203.

机构信息

Department of Internal Medicine, Faculty of Medicine, Suleyman Demirel University, Cunur, Turkey.

Division of Endocrinology, Department of Internal Medicine, Faculty of Medicine, Suleyman Demirel University, Cunur, Turkey -

出版信息

Minerva Endocrinol (Torino). 2022 Sep;47(3):314-324. doi: 10.23736/S2724-6507.20.03204-6. Epub 2020 Dec 17.

DOI:10.23736/S2724-6507.20.03204-6
PMID:33331738
Abstract

BACKGROUND

The aim of this study was to evaluate changes in the serum levels of miR-98, miR-184, miR-185, miR-203 and miR-196a-3p in type 2 diabetes mellitus (T2DM) patients with diabetic nephropathy (DN) and to associate the changes in microRNA levels with urinary albumin excretion (UAE).

METHODS

The study included 35 healthy individuals aged between 18-65 years, 40 T2DM patients with normoalbuminuria, 40 T2DM patients with microalbuminuria, and 35 T2DM patients with macroalbuminuria. Metabolic laboratory parameters, microalbumin levels in 24-hour urine samples were measured in all groups. Serum levels of vascular endothelial growth factor-A (VEGF-A) and transforming growth factor-β (TGF-β) were measured quantitatively by Enzyme-Linked Immunosorbent Assay (ELISA). Circulating miRNA levels were determined by real-time quantitative PCR.

RESULTS

Serum miR-196a-3p levels were reduced in the normoalbuminuria group compared to the healthy control group. In the macroalbuminuria and microalbuminuria groups, miR-196a-3p levels were higher compared to the normoalbuminuria group. In addition, increase in miR-196a-3p levels in the macroalbuminuria group was more prominent than the microalbuminuria group. Serum miR-203 levels were significantly higher in the macroalbuminuria group compared to healthy controls, microalbuminuria and normoalbuminuria groups; these levels were also higher in the microalbuminuria group compared to normoalbuminuria group. In logistic regression analysis, serum miR-196a-3p and miRNA-203 levels were independently correlated to UAE.

CONCLUSIONS

Increased serum levels of miR-203 and miR-196a-3p are independent risk factors of UAE which is a marker of DN.

摘要

背景

本研究旨在评估血清 miR-98、miR-184、miR-185、miR-203 和 miR-196a-3p 在 2 型糖尿病伴糖尿病肾病(DN)患者中的变化,并将 miRNA 水平的变化与尿白蛋白排泄(UAE)相关联。

方法

本研究纳入了 35 名年龄在 18-65 岁之间的健康个体、40 名无白蛋白尿的 2 型糖尿病患者、40 名微量白蛋白尿的 2 型糖尿病患者和 35 名大量白蛋白尿的 2 型糖尿病患者。所有组均测量代谢实验室参数和 24 小时尿样中的微量白蛋白水平。通过酶联免疫吸附测定(ELISA)定量测量血清血管内皮生长因子-A(VEGF-A)和转化生长因子-β(TGF-β)水平。通过实时定量 PCR 测定循环 miRNA 水平。

结果

与健康对照组相比,正常白蛋白尿组血清 miR-196a-3p 水平降低。在大量白蛋白尿和微量白蛋白尿组中,miR-196a-3p 水平高于正常白蛋白尿组。此外,与微量白蛋白尿组相比,大量白蛋白尿组 miR-196a-3p 水平的升高更为明显。与健康对照组、微量白蛋白尿组和正常白蛋白尿组相比,大量白蛋白尿组血清 miR-203 水平显著升高;与正常白蛋白尿组相比,微量白蛋白尿组血清 miR-203 水平也升高。在逻辑回归分析中,血清 miR-196a-3p 和 miRNA-203 水平与 UAE 独立相关。

结论

血清 miR-203 和 miR-196a-3p 水平升高是 UAE 的独立危险因素,UAE 是 DN 的标志物。

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