TY - JOUR
T1 - Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes
AU - Ghai, Vikas
AU - Wu, Xiaogang
AU - Bheda-Malge, Anjalei
AU - Argyropoulos, Christos P.
AU - Bernardo, José F.
AU - Orchard, Trevor
AU - Galas, David
AU - Wang, Kai
N1 - Funding Information:
We thank Inyoul Lee, Kathie Walters, and Mary Brunkow for feedback on the manuscript, and Taek-Kyun Kim, Minyoung Lee, David Baxter, and Alton Etheridge for technical advice. Funding was provided by National Institutes of Health (NIH)/DK34818 (TO), The Rossi Memorial Fund (TO, and NIH U01/RFA-RM-13-014 (DG and KW).
Publisher Copyright:
© 2017 International Society of Nephrology
PY - 2018/5
Y1 - 2018/5
N2 - 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-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.
AB - 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-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.
KW - RNA-seq
KW - diabetic nephropathy
KW - extracellular vesicles
KW - microRNAs
KW - microalbuminuria
UR - http://www.scopus.com/inward/record.url?scp=85044755714&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85044755714&partnerID=8YFLogxK
U2 - 10.1016/j.ekir.2017.11.019
DO - 10.1016/j.ekir.2017.11.019
M3 - Article
C2 - 29854963
AN - SCOPUS:85044755714
SN - 2468-0249
VL - 3
SP - 555
EP - 572
JO - Kidney International Reports
JF - Kidney International Reports
IS - 3
ER -