Advanced oxidation protein products promote inflammation in diabetic kidney through activation of renal nicotinamide adenine dinucleotide phosphate oxidase.
The involvement of inflammatory processes has been recognized in development and/or progression of diabetic nephropathy. However, the mechanisms involved in the pathogenesis of renal inflammation have not been completely understood. In this study, we tested the hypothesis that accumulation of advanced oxidation protein products (AOPPs), which occurs in diabetes, may promote inflammatory responses in diabetic kidney. Streptozotocin-induced diabetic rats were randomized to iv injection of vehicle, native rat serum albumin (RSA), and AOPPs-modified RSA (AOPPs-RSA) in the presence or absence of oral administration of apocynin. A control group was followed concurrently. Compared with RSA- or vehicle-treated diabetic rats, AOPPs-RSA-treated animals displayed significant increase in renal macrophage infiltration and overexpression of monocyte chemoattractant protein-1 and TGF-beta1. This was associated with deteriorated structural and functional abnormalities of diabetic kidney, such as glomerular hypertrophy, fibronectin accumulation, and albuminuria. AOPP challenge significantly increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide generation in renal homogenates and up-regulated membrane expression of renal NADPH oxidase subunits p47(phox) and gp91(phox). All these AOPPs-induced perturbations in diabetic kidney could be prevented by the NADPH oxidase inhibitor apocynin. These data suggest that chronic accumulation of AOPPs may promote renal inflammation in diabetes probably through activation of renal NADPH oxidase.
Shi
Xiao Yun
XY
Division of Nephrology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, People's Republic of China.
Hou
Fan Fan
FF
Niu
Hong Xin
HX
Wang
Guo Bao
GB
Xie
Di
D
Guo
Zhi Jian
ZJ
Zhou
Zhan Mei
ZM
Yang
Fang
F
Tian
Jian Wei
JW
Zhang
Xun
X
D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics; D003928:Diabetic Nephropathies / Q000209:etiology*; D004789:Enzyme Activation; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008297:Male; D019255:NADPH Oxidases / Q000502:physiology*; D009393:Nephritis / Q000209:etiology*; D010084:Oxidation-Reduction; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000235:genetics
C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D011506:Proteins; D053773:Transforming Growth Factor beta1; D019255:NADPH Oxidases