title: The role of adenosine receptors A2A and A2B signaling in renal fibrosis.
abstract: Renal fibrosis, the key histopathological lesion in the development and progression of chronic kidney disease (CKD), has been the focus of much research in recent decades. The growing burden of CKD in both developed and developing nations highlights a need for novel therapies to halt the progression of renal disease. Insights into the pathogenesis of renal fibrosis and the key cellular and molecular mediators have been critical in the process of identifying potential targets of therapy. Adenosine signaling is an innate biological autocrine and paracrine cellular signaling pathway involving several key mediators: ectonucleotidases, adenosine, and adenosine receptors. Short-term activation of the adenosine A2A and A2B receptors decreases inflammation, which precedes renal fibrosis. However, in conditions of persistent, excessive adenosine exposure, such as in patients born with adenosine deaminase (ADA) deficiency, adenosine signaling via A2B receptor promotes renal fibrosis, as seen in chronic inflammation. This review will describe the increasingly recognized complex role of adenosine signaling in the development of renal fibrosis. We will speculate how the knowledge gained may be employed in the search for more effective therapies based on these complex signaling pathways.
authors: Immunology Research Centre, St Vincent's Hospital Melbourne and Department of Medicine, University of Melbourne, Melbourne, Australia.
authors: Veena S
authors: VS
authors: Roberts
authors: Immunology Research Centre, St Vincent's Hospital Melbourne and Department of Medicine, University of Melbourne, Melbourne, Australia.
authors: Peter J
authors: PJ
authors: Cowan
authors: Centre for Kidney Research, Children's Hospital at Westmead, Sydney, Australia.
authors: Stephen I
authors: SI
authors: Alexander
authors: Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors: Simon C
authors: SC
authors: Robson
authors: Immunology Research Centre, St Vincent's Hospital Melbourne and Department of Medicine, University of Melbourne, Melbourne, Australia.
authors: Karen M
authors: KM
authors: Dwyer
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001081:Apyrase / Q000378:metabolism; D019898:Autocrine Communication; D005347:Fibroblasts; D005355:Fibrosis; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology*; D008264:Macrophages; D019899:Paracrine Communication; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D043704:Receptor, Adenosine A2B / Q000378:metabolism*; D051436:Renal Insufficiency, Chronic / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction
chemical_list: D015703:Antigens, CD; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D000251:Adenosine Triphosphatases; C027201:ectoATPase; C518948:nucleoside triphosphate diphosphohydrolase 8, human; D001081:Apyrase; C067869:CD39 antigen; D000241:Adenosine