Reduced adenosine uptake and its contribution to signaling that mediates profibrotic activation in renal tubular epithelial cells: Implication in diabetic nephropathy
Por:
Kretschmar C., Oyarzún C., Villablanca C., Jaramillo C., Alarcón S., Perez G., Díaz-Encarnación M.M., Pastor-Anglada M., Garrido W., Quezada C., Martín R.S.
Publicada:
1 ene 2016
Resumen:
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.
Filiaciones:
Kretschmar C.:
Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile
Oyarzún C.:
Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile
Villablanca C.:
Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile
Jaramillo C.:
Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile
Alarcón S.:
Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile
Perez G.:
Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile
Díaz-Encarnación M.M.:
Nephrology Service Fundació Puigvert, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain
Pastor-Anglada M.:
Institute of Biomedicine and Oncology Programme, National Biomedical Research Institute of Liver and Gastrointestinal Diseases (CIBER EHD), Department of Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain
Garrido W.:
Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile
Quezada C.:
Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile
Martín R.S.:
Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile
Gold
|