2-chloro-n(6)-(3-iodobenzyl)adenosine-5--n-methyluronamide and Polycystic-Kidney--Autosomal-Dominant

ADPKD is a renal pathology caused by mutations of PKD1 and PKD2 genes, which encode for polycystin-1 (PC1) and polycystin-2 (PC2), respectively. PC1 plays an important role regulating several signal transducers, including cAMP and mTOR, which are involved in abnormal cell proliferation of ADPKD cells leading to the development and expansion of kidney cysts that are a typical hallmark of this disease. Therefore, the inhibition of both pathways could potentiate the reduction of cell proliferation enhancing benefits for ADPKD patients.. The inhibition of cAMP- and mTOR-related signalling was performed by Cl-IB-MECA, an agonist of A3 receptors, and rapamycin, respectively. Protein kinase activity was evaluated by immunoblot and cell growth was analyzed by direct cell counting.. The activation of A. The double treatment with rapamycin and Cl-IB-MECA may have synergistic effects on the inhibition of cell proliferation in ADPKD cells suggesting that combined therapies could improve renal function in ADPKD patients.

Topics: Adenosine; Adenosine A3 Receptor Agonists; Animals; Cell Line; Cell Proliferation; CREB-Binding Protein; Cyclic AMP; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Extracellular Signal-Regulated MAP Kinases; Genetic Predisposition to Disease; Humans; Kidney; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Phosphorylation; Polycystic Kidney, Autosomal Dominant; Protein Kinase Inhibitors; Signal Transduction; Sirolimus; Time Factors; TOR Serine-Threonine Kinases; TRPP Cation Channels