Hong-Zhao Xu1, Wan-Ning Wang1, Yuan-Yuan Zhang1, Yan-Li Cheng1, Zhong-Gao Xu2. 1. Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin, China. 2. Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin, China. renalxu@163.com.
Abstract
BACKGROUND: The 12-lipoxygenase (12-LO) and angiotensin II (Ang II) interaction plays an important role in diabetic nephropathy (DN). Proteinuria in DN is associated with decreased slit diaphragm proteins including nephrin and P-cadherin. Therefore, we investigated whether Ang II type 1 receptor (AT1) blocker (ARB) regulates 12-LO activity and slit diaphragm protein expression in diabetic rat glomeruli. METHOD: Glomeruli were isolated with the sieving method, and classified into small glomeruli (SG; 75-μm sieve) and large glomeruli (LG; 125-μm sieve). RESULTS: 12(S)-HETE, a lipid product of 12-LO, was increased by Ang II in the glomeruli. Infusion of 12(S)-HETE and Ang II significantly decreased nephrin expression in LG, but increased it in SG compared to control. Glomerular P-cadherin expression was reduced after Ang II and 12(S)-HETE treatment without differences between LG and SG. ARB did not influence glycemic levels but completely abolished the increases in 12(S)-HETE, AT1 expression, and proteinuria in diabetic rats. Nephrin expression was significantly reduced in LG but increased in SG in diabetic rats compared to control. P-cadherin expression decreased in both diabetic LG and SG. The abnormalities of nephrin and P-cadherin were partially but significantly reversed by ARB. CONCLUSION: ARB potentially ameliorates DN via the up-regulation of glomerular nephrin and P-cadherin expression through the inhibition of 12-LO activation in the glomeruli of rats with DN.
BACKGROUND: The 12-lipoxygenase (12-LO) and angiotensin II (Ang II) interaction plays an important role in diabetic nephropathy (DN). Proteinuria in DN is associated with decreased slit diaphragm proteins including nephrin and P-cadherin. Therefore, we investigated whether Ang II type 1 receptor (AT1) blocker (ARB) regulates 12-LO activity and slit diaphragm protein expression in diabeticrat glomeruli. METHOD: Glomeruli were isolated with the sieving method, and classified into small glomeruli (SG; 75-μm sieve) and large glomeruli (LG; 125-μm sieve). RESULTS: 12(S)-HETE, a lipid product of 12-LO, was increased by Ang II in the glomeruli. Infusion of 12(S)-HETE and Ang II significantly decreased nephrin expression in LG, but increased it in SG compared to control. Glomerular P-cadherin expression was reduced after Ang II and 12(S)-HETE treatment without differences between LG and SG. ARB did not influence glycemic levels but completely abolished the increases in 12(S)-HETE, AT1 expression, and proteinuria in diabeticrats. Nephrin expression was significantly reduced in LG but increased in SG in diabeticrats compared to control. P-cadherin expression decreased in both diabetic LG and SG. The abnormalities of nephrin and P-cadherin were partially but significantly reversed by ARB. CONCLUSION: ARB potentially ameliorates DN via the up-regulation of glomerular nephrin and P-cadherin expression through the inhibition of 12-LO activation in the glomeruli of rats with DN.
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