Linagliptin and telmisartan induced effects on renal and urinary exosomal miRNA expression in rats with 5/6 nephrectomy.
Angiotensin II Type 1 Receptor Blockers
/ pharmacology
Animals
Dipeptidyl-Peptidase IV Inhibitors
/ pharmacology
Exosomes
/ metabolism
Gene Expression Regulation
/ drug effects
Kidney
/ metabolism
Linagliptin
/ pharmacology
MicroRNAs
/ metabolism
Nephrectomy
Principal Component Analysis
RNA, Messenger
/ metabolism
Rats
Rats, Wistar
Telmisartan
/ pharmacology
Urinary Tract
/ metabolism
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
25 02 2020
25 02 2020
Historique:
received:
04
10
2019
accepted:
11
02
2020
entrez:
27
2
2020
pubmed:
27
2
2020
medline:
21
11
2020
Statut:
epublish
Résumé
Dipeptidyl peptidase 4 inhibitors and angiotensin II receptor blockers attenuate chronic kidney disease progression in experimental diabetic and non-diabetic nephropathy in a blood pressure and glucose independent manner, but the exact molecular mechanisms remain unclear. MicroRNAs (miRNAs) are short, non-coding RNA species that are important post-transcriptional regulators of gene expression and play an important role in the pathogenesis of nephropathy. miRNAs are present in urine in a remarkably stable form, packaged in extracellular vesicles. Here, we investigated linagliptin and telmisartan induced effects on renal and urinary exosomal miRNA expression in 5/6 nephrectomized rats. In the present study, renal miRNA profiling was conducted using the Nanostring nCounter technology and mRNA profiling using RNA sequencing from the following groups of rats: sham operated plus placebo; 5/6 nephrectomy plus placebo; 5/6 nephrectomy plus telmisartan; and 5/6 nephrectomy plus linagliptin. TaqMan Array miRNA Cards were used to evaluate which of the deregulated miRNAs in the kidney are present in urinary exosomes. In kidneys from 5/6 nephrectomized rats, the expression of 13 miRNAs was significantly increased (>1.5-fold, P < 0.05), whereas the expression of 7 miRNAs was significantly decreased (>1.5-fold, P < 0.05). Most of the deregulated miRNA species are implicated in endothelial-to-mesenchymal transition and inflammatory processes. Both telmisartan and linagliptin suppressed the induction of pro-fibrotic miRNAs, such as miR-199a-3p, and restored levels of anti-fibrotic miR-29c. In conclusion, the linagliptin and telmisartan-induced restorative effects on miR-29c expression were reflected in urinary exosomes, suggesting that miRNA profiling of urinary exosomes might be used as a biomarker for CKD progression and monitoring of treatment effects.
Identifiants
pubmed: 32099009
doi: 10.1038/s41598-020-60336-4
pii: 10.1038/s41598-020-60336-4
pmc: PMC7042229
doi:
Substances chimiques
Angiotensin II Type 1 Receptor Blockers
0
Dipeptidyl-Peptidase IV Inhibitors
0
MicroRNAs
0
RNA, Messenger
0
Linagliptin
3X29ZEJ4R2
Telmisartan
U5SYW473RQ
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3373Références
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