Reduced adenosine uptake and its contribution to signaling that mediates profibrotic activation in renal tubular epithelial cells: Implication in diabetic nephropathy

Autor: Kretschmar C, Oyarzún C, Villablanca C, Jaramillo C, Alarcón S, Perez G, Díaz-Encarnación MM, Pastor-Anglada M, Garrido W, Quezada C, San Martín R
Rok vydání: 2016
Předmět:
Zdroj: PLoS One
r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
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r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
Fundació Sant Joan de Déu
r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
ISSN: 1932-6203
Popis: 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-ß and the general adenosine receptor agonist NECA, induced the expression of profibrotic cell activation markers a-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 a-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. Copyright: © 2016 Kretschmar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Databáze: OpenAIRE