| Autor: |
Delić D; Boehringer Ingelheim Pharma GmbH & Co. KG, Translational Medicine & Clinical Pharmacology, Biberach, Germany. denis.delic@boehringer-ingelheim.com., Wiech F; Boehringer Ingelheim Pharma GmbH & Co. KG, Translational Medicine & Clinical Pharmacology, Biberach, Germany., Urquhart R; Boehringer Ingelheim Pharma GmbH & Co. KG, Translational Medicine & Clinical Pharmacology, Biberach, Germany., Gabrielyan O; Boehringer Ingelheim Pharma GmbH & Co. KG, Translational Medicine & Clinical Pharmacology, Biberach, Germany., Rieber K; Boehringer Ingelheim Pharma GmbH & Co. KG, Translational Medicine & Clinical Pharmacology, Biberach, Germany., Rolser M; Boehringer Ingelheim Pharma GmbH & Co. KG, Translational Medicine & Clinical Pharmacology, Biberach, Germany., Tsuprykov O; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany., Hasan AA; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany.; Department of Biochemistry, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt., Krämer BK; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany., Baum P; Boehringer Ingelheim Pharma GmbH & Co. KG, Translational Medicine & Clinical Pharmacology, Biberach, Germany., Köhler A; Boehringer Ingelheim Pharma GmbH & Co. KG, Translational Medicine & Clinical Pharmacology, Biberach, Germany., Gantner F; Boehringer Ingelheim Pharma GmbH & Co. KG, Translational Medicine & Clinical Pharmacology, Biberach, Germany., Mark M; Boehringer Ingelheim Pharma GmbH & Co. KG, Cardiometabolic Diseases Research, Biberach, Germany., Hocher B; Fifth Department of Medicine (Nephrology/Endocrinology/Rheumatology), University Medical Centre Mannheim, University of Heidelberg, Heidelberg, Germany. berthold.hocher@medma.uni-heidelberg.de., Klein T; Boehringer Ingelheim Pharma GmbH & Co. KG, Cardiometabolic Diseases Research, Biberach, Germany. |
| Abstrakt: |
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. |
