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oai:recercat.cat:2445/1045252025-12-04T21:12:56Zcom_2072_1057col_2072_478781col_2072_478917

Reduced adenosine uptake and its contribution to signaling that mediates profibrotic activation in renal tubular epithelial cells: implication in diabetic nephropathy. Kretschmar, Catalina Oyarzún, Carlos Villablanca, Cristopher Jaramillo, Catherinne Alarcón, Sebastián Perez, Gustavo Díaz-Encarnación, Montserrat M. M. Pastor Anglada, Marçal Garrido, Wallys Quezada, Claudia San Martín, Rody Diabetis Cèl·lules epitelials Adenosina Diabetes Epithelial cells Adenosine Altered nucleoside levels may be linked to pathogenic signaling through adenosine recep- tors. We hypothesized that adenosine dysregulation contributes to fibrosis in diabetic kid- ney disease. Our findings indicate that high glucose levels and experimental diabetes decreased uptake activity through the equilibrative nucleoside transporter 1 (ENT1) in proxi- mal 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 A 3 receptor subtype in vitro. Furthermore, induction of fibrosis marker α -SMA was prevented by the A 3 receptor antagonist in diabetic rat kidneys. In conclusion, we evidenced the contribution of purinergic signaling to renal fibrosis in experimental diabetic nephropathy. 2016-12-07T13:11:58Z 2016-12-07T13:11:58Z 2016-01-25 2016-12-07T13:12:03Z info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion 1932-6203 https://hdl.handle.net/2445/104525 663309 26808537 eng Reproducció del document publicat a: https://doi.org/10.1371/journal.pone.0147430 PLoS One, 2016, vol. 11, num. 1, p. e0147430 https://doi.org/10.1371/journal.pone.0147430 cc-by (c) Kretschmar, Catalina et al., 2016 http://creativecommons.org/licenses/by/3.0/es info:eu-repo/semantics/openAccess 20 p. application/pdf Public Library of Science (PLoS) Articles publicats en revistes (Bioquímica i Biomedicina Molecular)