Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes

被引:60
作者
Ghai, Vikas [1 ]
Wu, Xiaogang [1 ]
Bheda-Malge, Anjalei [1 ]
Argyropoulos, Christos P. [2 ]
Bernardo, Jose F. [3 ]
Orchard, Trevor [3 ]
Galas, David [4 ]
Wang, Kai [1 ]
机构
[1] Inst Syst Biol, 401 Terry Ave N, Seattle, WA 98109 USA
[2] Univ New Mexico, Dept Nephrol, Albuquerque, NM 87131 USA
[3] Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA USA
[4] Pacific Northwest Res Inst, Seattle, WA USA
来源
KIDNEY INTERNATIONAL REPORTS | 2018年 / 3卷 / 03期
基金
美国国家卫生研究院;
关键词
diabetic nephropathy; extracellular vesicles; microalbuminuria; microRNAs; RNA-seq; PROMOTES RENAL FIBROSIS; EPITHELIAL-MESENCHYMAL TRANSITION; EXOSOME-MEDIATED TRANSFER; CIRCULATING MICRORNAS; INSULIN SENSITIVITY; DOWN-REGULATION; CARDIOVASCULAR-DISEASE; POTENTIAL BIOMARKERS; MOLECULAR-MECHANISMS; ENDOTHELIAL FUNCTION;
D O I
10.1016/j.ekir.2017.11.019
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Introduction: 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. Methods: 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. Results: 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. Conclusion: Many of the miRNAs associated with DN occurrence or MA status directly target pathways associated with renal fibrosis (including transforming growth factor-beta 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.
引用
收藏
页码:555 / 572
页数:18
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