title: Reduced Adenosine Uptake and Its Contribution to Signaling that Mediates Profibrotic Activation in Renal Tubular Epithelial Cells: Implication in Diabetic Nephropathy.
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.
authors.affiliation: Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Catalina
authors.initials: C
authors.lastname: Kretschmar
authors.affiliation: Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Carlos
authors.initials: C
authors.lastname: Oyarzún
authors.affiliation: Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Cristopher
authors.initials: C
authors.lastname: Villablanca
authors.affiliation: Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Catherinne
authors.initials: C
authors.lastname: Jaramillo
authors.affiliation: Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Sebastián
authors.initials: S
authors.lastname: Alarcón
authors.affiliation: Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Perez
authors.affiliation: Nephrology Service Fundació Puigvert, Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain.
authors.forename: Montserrat M
authors.initials: MM
authors.lastname: Díaz-Encarnación
authors.affiliation: 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.
authors.forename: Marçal
authors.initials: M
authors.lastname: Pastor-Anglada
authors.affiliation: Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Wallys
authors.initials: W
authors.lastname: Garrido
authors.affiliation: Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Claudia
authors.initials: C
authors.lastname: Quezada
authors.affiliation: Institute of Biochemistry and Microbiology, Science Faculty, Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Rody
authors.initials: R
authors.lastname: San Martín
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003928:Diabetic Nephropathies / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism*; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction
chemical_list: D000241:Adenosine