title: Increased adenosine levels contribute to ischemic kidney fibrosis in the unilateral ureteral obstruction model.
abstract: Renal interstitial fibrosis (RIF) occurs as a result of chronic kidney disease (CKD) and is a common pathway leading to end-stage renal failure. Renal tissue hypoxia and ischemia are present during CKD. Adenosine (ADO) is an important signaling molecule induced under ischemic and hypoxic conditions. In the present study, the association between ADO and RIF was investigated using a mouse model, with the aim of obtaining important information relevant to the prevention and treatment of RIF. A unilateral ureteral obstruction (UUO) model of RIF was established in mice. A total of 44 male mice were randomly divided into sham, model and intervention groups, and samples were collected on days 1, 3, 7, and 14 after modeling. These were collected to detect hypoxia and changes in ADO concentration in obstructed renal tissue as well as to analyze the pathological changes and degree of RIF in the renal tissue. Changes in the levels of collagen deposition and profibrogenic factors in renal tissues were analyzed following intervention with an ADO receptor blocker. Following the UUO procedure, continuous hypoxia was present in the obstructed renal tissue, accompanied by an increased ADO concentration. Tubular injury and interstitial fibrosis progressively increased over time following the UUO procedure. The mRNA expression levels of tissue tumor growth factor β1(TGF-β1) and α1(I) procollagen were significantly increased. Subsequent to the ADO pathway being blocked by 8-(p-sulfophenyl)-theophylline, tubular injury and interstitial fibrosis were reduced and the expression of related cytokines was decreased. Increased ADO levels were induced by hypoxia, causing the development of RIF. Following the blocking of the ADO pathway, renal damage was deferred and renal functions were protected.
authors: Department of Urology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors: Jin
authors: J
authors: Tang
authors: Department of Urology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors: Xianzhen
authors: X
authors: Jiang
authors: Department of Urology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors: Yihong
authors: Y
authors: Zhou
authors: Department of Urology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors: Bing
authors: B
authors: Xia
authors: Department of Urology, The Third Xiangya Hospital of Central South University, Changsha, Hunan 410013, P.R. China.
authors: Yingbo
authors: Y
authors: Dai
keywords: adenosine; cytokines; renal interstitial fibrosis; unilateral ureteral obstruction model; α-smooth muscle actin