Reduced Adenosine Uptake and Its Contribution to Signaling that Mediates Profibrotic Activation in Renal Tubular Epithelial Cells: Implication in Diabetic Nephropathy

PloS One
Catalina KretschmarRody San Martín

Abstract

Altered nucleoside levels may be linked to pathogenic signaling through adenosine receptors. We hypothesized that adenosine dysregulation contributes to fibrosis in diabetic kidney disease. Our findings indicate that high glucose levels and experimental diabetes decreased uptake activity through the equilibrative nucleoside transporter 1 (ENT1) in proximal tubule cells. In addition, a correlation between increased plasma content of adenosine and a marker of renal fibrosis in diabetic rats was evidenced. At the cellular level, exposure of HK2 cells to high glucose, TGF-β and the general adenosine receptor agonist NECA, induced the expression of profibrotic cell activation markers α-SMA and fibronectin. These effects can be avoided by using a selective antagonist of the adenosine A3 receptor subtype in vitro. Furthermore, induction of fibrosis marker α-SMA was prevented by the A3 receptor antagonist in diabetic rat kidneys. In conclusion, we evidenced the contribution of purinergic signaling to renal fibrosis in experimental diabetic nephropathy.

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Citations

Mar 3, 2017·British Journal of Pharmacology·Pier Andrea BoreaKatia Varani
Jan 18, 2017·Journal of Cellular and Molecular Medicine·Minna LiuQi Qian
Feb 20, 2018·Nature Reviews. Nephrology·Josephine M Forbes, David R Thorburn
Mar 16, 2018·Purinergic Signalling·A M RodriguesElisa Mieko Suemitsu Higa
Oct 11, 2017·Frontiers in Pharmacology·Geoffrey Burnstock
Jul 3, 2018·Frontiers in Pharmacology·Marçal Pastor-Anglada, Sandra Pérez-Torras
Jun 3, 2021·International Journal of Molecular Sciences·Eun Seon PakHunjoo Ha

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Datasets Mentioned

BETA
AM16708

Methods Mentioned

BETA
biopsies
protein assay
transfection

Software Mentioned

SCANIT
UN

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