title: Advanced oxidation protein products promote inflammation in diabetic kidney through activation of renal nicotinamide adenine dinucleotide phosphate oxidase.
abstract: 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.
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, People's Republic of China.
authors.forename: Xiao Yun
authors.initials: XY
authors.lastname: Shi
authors.forename: Fan Fan
authors.initials: FF
authors.lastname: Hou
authors.forename: Hong Xin
authors.initials: HX
authors.lastname: Niu
authors.forename: Guo Bao
authors.initials: GB
authors.lastname: Wang
authors.forename: Di
authors.initials: D
authors.lastname: Xie
authors.forename: Zhi Jian
authors.initials: ZJ
authors.lastname: Guo
authors.forename: Zhan Mei
authors.initials: ZM
authors.lastname: Zhou
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Jian Wei
authors.initials: JW
authors.lastname: Tian
authors.forename: Xun
authors.initials: X
authors.lastname: Zhang
mesh_terms: 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
chemical_list: C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D011506:Proteins; D053773:Transforming Growth Factor beta1; D019255:NADPH Oxidases