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Angiotensin II increases oxidative stress and induces glomerular sclerosis via toll-like receptor 4

The bulletin of the Yamaguchi Medical School Volume 63 Issue 1-2 Page 25-34
published_at 2016
A050063000104.pdf
[fulltext] 1.77 MB
Title
Angiotensin II increases oxidative stress and induces glomerular sclerosis via toll-like receptor 4
Abstract
Background: Angiotensin II (AngII) increases reactive oxygen species (ROS) and induces glomerular sclerosis. Toll-like receptor 4 (TLR4)-mediated inflammation enhances the renal impairment in renal inflammatory diseases. The relationship between TLR4 and AngII-induced glomerular sclerosis is unknown.Methods: Mice lacking TLR4 function (Tlr4^{lps-d}) and wild-type (WT) mice were randomized into groups treated with AngII, norepinephrine (NE) or a sub-depressor dose of the AngII receptor blocker irbesartan along with AngII for 2 weeks. We then assessed the expressions of NADPH oxidase and monocyte chemoattractant protein-1 (MCP-1) and the inflammatory cell recruitment in the glomeruli. We also evaluated the mesangial matrix proliferation and ROS.Results: AngII and NE equally increased the systolic blood pressure compared to the control mice (p<0.05). In the WT mice treated with AngII, we observed glomerular sclerosis, an increase in NADPH oxidase, MCP-1 and the infiltration of macrophages as well as ROS content in the glomeruli compared to the control mice (p<0.05), whereas the Tlr4^{lps-d} mice showed little effects of AngII on these indices. In addition, the sub-depressor-dose irbesartan treatment reversed these changes. NE had little effects on these indices. Conclusions: TLR4 plays an important role in AngII-induced oxidative stress, inflammation and glomerular sclerosis through the AT1 receptor.
Creators Okamoto Tadashi
Creators Umemoto Seiji
Creators Yoshimura Koichi
Creators Sakumura Toshihiro
Creators Murata Tomoaki
Creators Fukai Tohru
Creators Yano Masafumi
Creators Matsuzaki Masanori
Affiliate Master Yamaguchi University
[kakenhi]15501 grid.268397.1
Source Identifiers [PISSN] 0513-1812 [NCID] AA00594272
Creator Keywords
glomerular sclerosis oxidative stress inflammation monocyte chemoattractant protein-1 angiotensin II
Resource Type departmental bulletin paper
Publishers Yamaguchi University School of Medicine
Date Issued 2016
File Version Version of Record
Access Rights open access
Schools 大学院医学系研究科(医学) 総合科学実験センター