title: A2B adenosine receptor-mediated induction of IL-6 promotes CKD.
abstract: Chronic elevation of adenosine, which occurs in the setting of repeated or prolonged tissue injury, can exacerbate cellular dysfunction, suggesting that it may contribute to the pathogenesis of CKD. Here, mice with chronically elevated levels of adenosine, resulting from a deficiency in adenosine deaminase (ADA), developed renal dysfunction and fibrosis. Both the administration of polyethylene glycol-modified ADA to reduce adenosine levels and the inhibition of the A(2B) adenosine receptor (A(2B)R) attenuated renal fibrosis and dysfunction. Furthermore, activation of A(2B)R promoted renal fibrosis in both mice infused with angiotensin II (Ang II) and mice subjected to unilateral ureteral obstruction (UUO). These three mouse models shared a similar profile of profibrotic gene expression in kidney tissue, suggesting that they share similar signaling pathways that lead to renal fibrosis. Finally, both genetic and pharmacologic approaches showed that the inflammatory cytokine IL-6 mediates adenosine-induced renal fibrosis downstream of A(2B)R. Taken together, these data suggest that A(2B)R-mediated induction of IL-6 contributes to renal fibrogenesis and shows potential therapeutic targets for CKD.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas-Houston Medical School, Houston, Texas, USA.
authors.forename: Yingbo
authors.initials: Y
authors.lastname: Dai
authors.forename: Weiru
authors.initials: W
authors.lastname: Zhang
authors.forename: Jiaming
authors.initials: J
authors.lastname: Wen
authors.forename: Yujin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rodney E
authors.initials: RE
authors.lastname: Kellems
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
mesh_terms: D000243:Adenosine Deaminase / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002908:Chronic Disease; D003094:Collagen / Q000096:biosynthesis; D005355:Fibrosis; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043704:Receptor, Adenosine A2B / Q000502:physiology*; D015398:Signal Transduction; D014517:Ureteral Obstruction / Q000150:complications
chemical_list: D015850:Interleukin-6; D043704:Receptor, Adenosine A2B; D000804:Angiotensin II; D003094:Collagen; D000243:Adenosine Deaminase