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Journal of Nephrology

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01-12-2016 | Original Article

Effect of angiotensin II type 1 receptor blocker on 12-lipoxygenase activity and slit diaphragm protein expression in type 2 diabetic rat glomeruli

Authors: Hong-zhao Xu, Wan-ning Wang, Yuan-yuan Zhang, Yan-li Cheng, Zhong-gao Xu

Published in: Journal of Nephrology | Issue 6/2016

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.

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Title: Effect of angiotensin II type 1 receptor blocker on 12-lipoxygenase activity and slit diaphragm protein expression in type 2 diabetic rat glomeruli
Authors: Hong-zhao Xu
Wan-ning Wang
Yuan-yuan Zhang
Yan-li Cheng
Zhong-gao Xu
Publication date: 01-12-2016
Publisher: Springer International Publishing
Published in: Journal of Nephrology / Issue 6/2016
Print ISSN: 1121-8428
Electronic ISSN: 1724-6059
DOI: https://doi.org/10.1007/s40620-016-0296-3

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