Adenosine A2A Receptor: A Target for Regulating Renal Interstitial Fibrosis in Obstructive Nephropathy

• DOI: 10.1371/journal.pone.0060173
• Publication Date: 2013-04-09T21:05:51Z
• Authors: Hang Xiao; Hai-Ying Shen; Wei Liu; Ren-ping Xiong; Ping Li; Gang Meng; Nan Yang; Xing Chen; Liang-Yi Si; Yuan-Guo Zhou
• Keywords: Adenosine A2A receptor

Renal interstitial fibrosis (RIF) is the common pathological process of chronic kidney diseases leading inevitably to renal function deterioration. RIF and its preceding epithelial-mesenchymal transition (EMT) are commonly triggered by an early occurring inflammation. However, effective approach prevent EMT still lacking urgent need. Recently, adenosine A2A receptor (A2AR) emerges as a novel inflammation regulator, therefore manipulation A2AR may suppress such protect against RIF. To test this hypothesis we applied unilateral ureteral obstruction (UUO) model on knockout mice their wild-type littermates, combined with intervention selective agonist, CGS 21680. On days 3, 7 14 post-UUO evaluated effects molecular progresses RIF, including cellular component infiltration, expression profibrotic factors, biomarkers EMT, collagen deposition extracellular matrix. Our data demonstrated that activation significantly suppressed types I III, reduced infiltration CD4+ T lymphocytes, attenuated TGF-β1 ROCK1, which in turn inhibited postponed progress. Conversely, genetic inactivation exacerbated aforementioned processes UUO-induced Together, effectively alleviated mice, suggesting potential therapeutic target for treatment