Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes.
Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes.
复制标题
DOI：
10.1016/j.ekir.2017.11.019
复制
发表时间：
2018-05
影响因子：
6
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Ghai V;Wu X;Bheda-Malge A;Argyropoulos CP;Bernardo JF;Orchard T;Galas D;Wang K
糖尿病肾病（DN）是一种进行性肾脏疾病，通常导致终末期肾脏疾病（ESRD）。它是由糖尿病引起的微血管并发症引起的。尽管微量白蛋白尿（MA）是1型糖尿病（T1 D）患者中DN的最早临床指征，但其缺乏检测早期DN的敏感性和特异性。最近，微小RNA（miRNAs）已经成为糖尿病以及各种形式的肾脏疾病（包括肾纤维化、急性肾损伤和进行性肾脏疾病）中的关键调节因子。此外，循环细胞外miRNA，特别是包装在细胞外囊泡（EV）中的miRNA，作为各种疾病和健康状况的潜在非侵入性生物标志物已经获得了显著的关注。作为匹兹堡大学糖尿病并发症流行病学（EDC）研究的一部分，在10年内以预先规定的时间间隔从患有不同级别DN或MA（正常，明显，间歇性和持续性）的T1 D个体中收集尿液。我们从尿液中分离EV并使用NextGen测序分析小RNA。与EV耗尽的样本相比，我们鉴定了一组在尿液EV中富集的miRNA，并鉴定了许多显示与DN发生、MA状态和其他变量（例如血红蛋白A1 c水平）相关的浓度变化的miRNA。许多与DN发生或MA状态相关的miRNA直接靶向与肾纤维化相关的途径（包括转化生长因子-β和磷酸酶和张力蛋白同源物），这是DN病理学的主要贡献者之一。这些miRNAs是DN和MA的潜在生物标志物。
Diabetic nephropathy (DN) is a form of progressive kidney disease that often leads to end-stage renal disease (ESRD). It is initiated by microvascular complications due to diabetes. Although microalbuminuria (MA) is the earliest clinical indication of DN among patients with type 1 diabetes (T1D), it lacks the sensitivity and specificity to detect the early onset of DN. Recently, microRNAs (miRNAs) have emerged as critical regulators in diabetes as well as various forms of kidney disease, including renal fibrosis, acute kidney injury, and progressive kidney disease. Additionally, circulating extracellular miRNAs, especially miRNAs packaged in extracellular vesicles (EVs), have garnered significant attention as potential noninvasive biomarkers for various diseases and health conditions. As part of the University of Pittsburgh Epidemiology of Diabetes Complications (EDC) study, urine was collected from individuals with T1D with various grades of DN or MA (normal, overt, intermittent, and persistent) over a decade at prespecified intervals. We isolated EVs from urine and analyzed the small-RNA using NextGen sequencing. We identified a set of miRNAs that are enriched in urinary EVs compared with EV-depleted samples, and identified a number of miRNAs showing concentration changes associated with DN occurrence, MA status, and other variables, such as hemoglobin A1c levels. Many of the miRNAs associated with DN occurrence or MA status directly target pathways associated with renal fibrosis (including transforming growth factor-β and phosphatase and tensin homolog), which is one of the major contributors to the pathology of DN. These miRNAs are potential biomarkers for DN and MA.
登录
查看更多内容
影响因子：
2.9
作者：
Cavero-Redondo I;Peleteiro B;Álvarez-Bueno C;Rodríguez-Artalejo F;Martínez-Vizcaíno V
通讯作者：
Martínez-Vizcaíno V
MicroRNA-LET-7A表达在NZB/W小鼠的肾小球细胞中增加，并在体外增加IL-6产生。
影响因子：
3.5
作者：
Chafin CB;Regna NL;Dai R;Caudell DL;Reilly CM
通讯作者：
Reilly CM
影响因子：
3.7
作者：
Barutta F;Tricarico M;Corbelli A;Annaratone L;Pinach S;Grimaldi S;Bruno G;Cimino D;Taverna D;Deregibus MC;Rastaldi MP;Perin PC;Gruden G
通讯作者：
Gruden G
ERK/MAPK 和 TGF-Beta/Smad 信号通路在血糖波动加速的糖尿病小鼠肾纤维化中发挥作用
影响因子：
4.3
作者：
Cheng X;Gao W;Dang Y;Liu X;Li Y;Peng X;Ye X
通讯作者：
Ye X
影响因子：
3.7
作者：
Bao L;Fu X;Si M;Wang Y;Ma R;Ren X;Lv H
通讯作者：
Lv H