Nan Sun1, Lei Zhai, Hui Li, Li-Hua Shi, Zhi Yao, Bo Zhang. 1. Department of Nephropathy, The Affiliated Hospital of Logistics University of the People's Armed Police Force, Tianjin, P. R. China.
Abstract
BACKGROUND/AIMS: The mechanism by which angiotensin-converting enzyme inhibitors (ACEIs) attenuate renal fibrosis has not been fully uncovered. METHODS: Renal fibrosis in rats was triggered by unilateral ureteral obstruction (UUO) and treated with Enalapril. RESULTS: Enalapril attenuated renal fibrosis, as evidenced by the fibrosis scores (1.07±0.73 versus 2.18±0.75 for 200 mg/ml Enalapril versus control, p<0.01) of Enalapril-treated UUO rats compared to mock-treated UUO rats. The amelioration was mast cell dependent, as Enalapril exhibited no effects on mast cell-deficient Kit(wsh/wsh) mice developing renal fibrosis. We detected lower levels of transforming growth factor β (TGF-β) and alpha-smooth muscle actin (α-SMA, a fibroblast activation marker) in the kidney tissue of Enalapril-treated UUO rats relative to the control UUO rats. Enalapril-treated UUO rats exhibited far fewer mast cells infiltrating per area in the kidney tissue than the control UUO rats (8.00±0.65 versus 29.00±0.57, p<0.01). Electron microscopy images revealed that mast cell degranulation was inhibited by Enalapril treatment. Further, IgE-mediated passive cutaneous anaphylaxis demonstrated that Enalapril blocked mast cell degranulation in vivo. CONCLUSION: Enalapril attenuated renal fibrosis in UUO rats, possibly by a mechanism involving the suppression of mast cell degranulation.
BACKGROUND/AIMS: The mechanism by which angiotensin-converting enzyme inhibitors (ACEIs) attenuate renal fibrosis has not been fully uncovered. METHODS:Renal fibrosis in rats was triggered by unilateral ureteral obstruction (UUO) and treated with Enalapril. RESULTS:Enalaprilattenuated renal fibrosis, as evidenced by the fibrosis scores (1.07±0.73 versus 2.18±0.75 for 200 mg/ml Enalapril versus control, p<0.01) of Enalapril-treated UUO rats compared to mock-treated UUO rats. The amelioration was mast cell dependent, as Enalapril exhibited no effects on mast cell-deficient Kit(wsh/wsh) mice developing renal fibrosis. We detected lower levels of transforming growth factor β (TGF-β) and alpha-smooth muscle actin (α-SMA, a fibroblast activation marker) in the kidney tissue of Enalapril-treated UUO rats relative to the control UUO rats. Enalapril-treated UUO rats exhibited far fewer mast cells infiltrating per area in the kidney tissue than the control UUO rats (8.00±0.65 versus 29.00±0.57, p<0.01). Electron microscopy images revealed that mast cell degranulation was inhibited by Enalapril treatment. Further, IgE-mediated passive cutaneous anaphylaxis demonstrated that Enalapril blocked mast cell degranulation in vivo. CONCLUSION:Enalaprilattenuated renal fibrosis in UUO rats, possibly by a mechanism involving the suppression of mast cell degranulation.
Authors: Onju Ham; William Jin; Lei Lei; Hui Hui Huang; Kenji Tsuji; Ming Huang; Jason Roh; Anthony Rosenzweig; Hua A Jenny Lu Journal: Sci Rep Date: 2018-10-31 Impact factor: 4.379