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High Glucose Induces Mesangial Cell Apoptosis through miR-15b-5p and Promotes Diabetic Nephropathy by Extracellular Vesicle Delivery.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2020 Mar 04; Vol. 28 (3), pp. 963-974. Date of Electronic Publication: 2020 Jan 15. - Publication Year :
- 2020
-
Abstract
- Diabetic nephropathy (DN) is an increasing threat to human health and is regarded as an important public issue. The pathophysiologic mechanisms of DN are complicated. The initiating molecular events triggering the loss function in mesangial cells (MCs) in DN are not well known. In this cross-disciplinary study, transcriptome analysis of high glucose (HG)-treated mouse MCs (MMCs) using next-generation sequencing and systematic bioinformatics analyses indicated that miR-15b-5p and its downstream target B cell lymphoma 2 (BCL-2) contribute to HG-induced apoptosis in MMCs. HG elevated miR-15b-5p expression, which in turn decreased the translation of BCL-2, leading to MMC apoptosis under HG. Apoptosis of MCs was enhanced in the presence of extracellular vesicles isolated from the urine of type 2 diabetic patients with high levels of miR-15b-5p. Furthermore, increased levels of urinary miR-15b-5p were found in db/db mice and type 2 diabetic patients, and such levels correlated with low baseline kidney function and rapid decline in kidney function during a mean of follow-up period of 2.4 ± 0.1 years. Therefore, miR-15b-5p induced mesangial cells apoptosis by targeting BCL-2 under HG. miR-15b-5p has the potential to predict kidney injury in DN. Blocking the miR-15b-5p epigenetic regulatory network could be a potential therapeutic strategy to prevent mesangial apoptosis in DN.<br /> (Copyright © 2020 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Biological Transport
Biomarkers
Cell Line
Diabetic Nephropathies pathology
Disease Susceptibility
Gene Expression Profiling
Gene Expression Regulation
Genes, bcl-2
Humans
Immunohistochemistry
Immunophenotyping
Mesangial Cells pathology
Mice
Models, Biological
RNA Interference
Apoptosis genetics
Blood Glucose
Diabetic Nephropathies etiology
Diabetic Nephropathies metabolism
Extracellular Vesicles metabolism
Glucose metabolism
Mesangial Cells metabolism
MicroRNAs genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0024
- Volume :
- 28
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 31991106
- Full Text :
- https://doi.org/10.1016/j.ymthe.2020.01.014