Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy
Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD). Elucidating the mechanisms underlying proteinuria in DKD is crucial because it is a common problem in DKD-related mortality and morbidity. MicroRNAs (miRs) associated with DKD have been detected in experimental diabe...
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doaj-5f8f7b3d2a9d454e86269635ea13d4302020-11-25T02:24:42ZengMDPI AGJournal of Clinical Medicine2077-03832020-04-0191220122010.3390/jcm9041220Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic NephropathyWen-Chin Lee0Lung-Chih Li1Hwee-Yeong Ng2Pei-Ting Lin3Terry Ting-Yu Chiou4Wei-Hung Kuo5Chien-Te Lee6Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDivision of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDiabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD). Elucidating the mechanisms underlying proteinuria in DKD is crucial because it is a common problem in DKD-related mortality and morbidity. MicroRNAs (miRs) associated with DKD have been detected in experimental diabetes models and in patients with both diabetes and CKD. Here, we aimed to investigate pathologic miRs in diabetic nephropathy (DN) by prospectively following six nephrotic, biopsy-proven isolated DN patients (enrolled between August 2015 and July 2017) for one year. The urinary exosomes were isolated at the time of the biopsy and the contained miRs were analyzed by next-generation sequencing. The results were compared to the control group, composed of age-, gender-, and CKD stage-matched patients with proteinuric CKD who did not present diabetes. Among the 72 identified miRs, we investigated eight (miR-188-5p, miR-150-3p, miR-760, miR-3677-3p, miR-548ah-3p, miR-548p, miR-320e, and miR-23c) exhibiting the strongest upregulation (13–15 fold) and two (miR-133a-3p and miR-153-3p) with the strongest downregulation (7–9 fold). The functional analysis of these miRs showed that they were involved in known and novel pathways of DN, supporting their pathologic roles. The bioinformatics-based prediction of the target genes of these miRs will inspire future research on the mechanisms underlying DN pathogenesis.https://www.mdpi.com/2077-0383/9/4/1220microRNAdiabetic nephropathynephrotic |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Wen-Chin Lee Lung-Chih Li Hwee-Yeong Ng Pei-Ting Lin Terry Ting-Yu Chiou Wei-Hung Kuo Chien-Te Lee |
spellingShingle |
Wen-Chin Lee Lung-Chih Li Hwee-Yeong Ng Pei-Ting Lin Terry Ting-Yu Chiou Wei-Hung Kuo Chien-Te Lee Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy Journal of Clinical Medicine microRNA diabetic nephropathy nephrotic |
author_facet |
Wen-Chin Lee Lung-Chih Li Hwee-Yeong Ng Pei-Ting Lin Terry Ting-Yu Chiou Wei-Hung Kuo Chien-Te Lee |
author_sort |
Wen-Chin Lee |
title |
Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy |
title_short |
Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy |
title_full |
Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy |
title_fullStr |
Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy |
title_full_unstemmed |
Urinary Exosomal MicroRNA Signatures in Nephrotic, Biopsy-Proven Diabetic Nephropathy |
title_sort |
urinary exosomal microrna signatures in nephrotic, biopsy-proven diabetic nephropathy |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2020-04-01 |
description |
Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD). Elucidating the mechanisms underlying proteinuria in DKD is crucial because it is a common problem in DKD-related mortality and morbidity. MicroRNAs (miRs) associated with DKD have been detected in experimental diabetes models and in patients with both diabetes and CKD. Here, we aimed to investigate pathologic miRs in diabetic nephropathy (DN) by prospectively following six nephrotic, biopsy-proven isolated DN patients (enrolled between August 2015 and July 2017) for one year. The urinary exosomes were isolated at the time of the biopsy and the contained miRs were analyzed by next-generation sequencing. The results were compared to the control group, composed of age-, gender-, and CKD stage-matched patients with proteinuric CKD who did not present diabetes. Among the 72 identified miRs, we investigated eight (miR-188-5p, miR-150-3p, miR-760, miR-3677-3p, miR-548ah-3p, miR-548p, miR-320e, and miR-23c) exhibiting the strongest upregulation (13–15 fold) and two (miR-133a-3p and miR-153-3p) with the strongest downregulation (7–9 fold). The functional analysis of these miRs showed that they were involved in known and novel pathways of DN, supporting their pathologic roles. The bioinformatics-based prediction of the target genes of these miRs will inspire future research on the mechanisms underlying DN pathogenesis. |
topic |
microRNA diabetic nephropathy nephrotic |
url |
https://www.mdpi.com/2077-0383/9/4/1220 |
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