Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients.
Humans
Diabetic Nephropathies
/ genetics
Transforming Growth Factor beta1
/ genetics
Epithelial-Mesenchymal Transition
/ genetics
Diabetes Mellitus, Type 2
/ complications
Up-Regulation
Endothelial Cells
Kidney
Extracellular Vesicles
/ genetics
MicroRNAs
/ genetics
Biomarkers
Glucose
Albumins
/ genetics
biomarkers
diabetic nephropathy
epithelial to mesenchymal transition
miRNAs
urinary extracellular vesicles
Journal
International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791
Informations de publication
Date de publication:
11 Oct 2022
11 Oct 2022
Historique:
received:
11
08
2022
revised:
03
10
2022
accepted:
06
10
2022
entrez:
27
10
2022
pubmed:
28
10
2022
medline:
29
10
2022
Statut:
epublish
Résumé
Diabetic nephropathy (DN) is a severe kidney-related complication of type 1 and type 2 diabetes and the most frequent cause of end-stage kidney disease. Extracellular vesicles (EVs) present in the urine mainly derive from the cells of the nephron, thus representing an interesting tool mirroring the kidney's physiological state. In search of the biomarkers of disease progression, we here assessed a panel of urinary EV miRNAs previously related to DN in type 2 diabetic patients stratified based on proteinuria levels. We found that during DN progression, miR145 and miR126 specifically increased in urinary EVs from diabetic patients together with albuminuria. In vitro, miRNA modulation was assessed in a model of TGF-β1-induced glomerular damage within a three-dimensional perfusion system, as well as in a model of tubular damage induced by albumin and glucose overload. Both renal tubular cells and podocytes undergoing epithelial to mesenchymal transition released EVs containing increased miR145 and miR126 levels. At the same time, miR126 levels were reduced in EVs released by glomerular endothelial cells. This work highlights a modulation of miR126 and miR145 during the progression of kidney damage in diabetes as biomarkers of epithelial to mesenchymal transition.
Identifiants
pubmed: 36292960
pii: ijms232012098
doi: 10.3390/ijms232012098
pmc: PMC9603196
pii:
doi:
Substances chimiques
Transforming Growth Factor beta1
0
MicroRNAs
0
Biomarkers
0
Glucose
IY9XDZ35W2
Albumins
0
MIRN145 microRNA, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
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