Xuelian Ma1,2, Yi Chang1,3, Yunzhao Xiong1,2, Zheng Wang3, Xiangting Wang2,3, Qingyou Xu4,5. 1. Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, China. 2. Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, China. 3. Department of Internal Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China. 4. Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Hebei University of Chinese Medicine, Shijiazhuang, China, qingyouxu@sohu.com. 5. Department of Internal Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China, qingyouxu@sohu.com.
Abstract
BACKGROUND: The progression of chronic renal failure in patients with unilateral renal injury is associated with loss of function in the contralateral kidney, but the molecular mechanism remains unclear. The activation of mineralocorticoid receptor (MR) in the kidney contributes to renal cell damage, leading to apoptosis, pyroptosis, and necrosis. Pyroptosis is a programmed cell death induced by caspase-1, which is usually activated by nod-like receptor pyrin-containing 3 (NLRP3) inflammasomes. Our study aimed to investigate the effects of eplerenone (EPL) on cell pyroptosis in the contralateral kidneys of unilateral ureteral obstruction (UUO) rats. METHODS: Sprague-Dawley rats were randomly divided into 3 groups: sham group, UUO group (10 days of left ureter ligation), and UUO treated with EPL (UUO + EPL) group. The contralateral kidneys of all rats were collected for studies. RESULTS: We observed evidently increased number of pyroptosis cells in the contralateral kidneys of UUO rats compared to those from Sham rats. The expression of NLRP3, caspase-1, interleukin-1β, serum and glucocorticoid-inducible protein kinase-1, and nuclear factor kappa B were also upregulated in the contralateral kidneys of UUO rats compared to Sham kidneys, and these effects were reduced by MR blocker EPL. CONCLUSION: Our data suggest that the activation of MR is involved in NLRP3/caspase-1 pathway-induced cell pyroptosis in the contralateral kidney of UUO model.
BACKGROUND: The progression of chronic renal failure in patients with unilateral renal injury is associated with loss of function in the contralateral kidney, but the molecular mechanism remains unclear. The activation of mineralocorticoid receptor (MR) in the kidney contributes to renal cell damage, leading to apoptosis, pyroptosis, and necrosis. Pyroptosis is a programmed cell death induced by caspase-1, which is usually activated by nod-like receptor pyrin-containing 3 (NLRP3) inflammasomes. Our study aimed to investigate the effects of eplerenone (EPL) on cell pyroptosis in the contralateral kidneys of unilateral ureteral obstruction (UUO) rats. METHODS:Sprague-Dawley rats were randomly divided into 3 groups: sham group, UUO group (10 days of left ureter ligation), and UUO treated with EPL (UUO + EPL) group. The contralateral kidneys of all rats were collected for studies. RESULTS: We observed evidently increased number of pyroptosis cells in the contralateral kidneys of UUO rats compared to those from Sham rats. The expression of NLRP3, caspase-1, interleukin-1β, serum and glucocorticoid-inducible protein kinase-1, and nuclear factor kappa B were also upregulated in the contralateral kidneys of UUO rats compared to Sham kidneys, and these effects were reduced by MR blocker EPL. CONCLUSION: Our data suggest that the activation of MR is involved in NLRP3/caspase-1 pathway-induced cell pyroptosis in the contralateral kidney of UUO model.