AGEs activate mesangial TGF-β–Smad signaling via an angiotensin II type I receptor interaction

Fukami, Kei; Ueda, Seinosuke; Yamagishi, Sho‐ichi; Kato, Seiya; Inagaki, Yoshishige; Takeuchi, Masayoshi; Motomiya, Yoshihiro; Bucala, Richard; Iida, Shuji; Tamaki, Kiyoshi; Imaizumi, Tsutomu; Cooper, Mark E.; Okuda, Seiya

doi:10.1111/j.1523-1755.2004.66004.x

Cited by 210 publications

(163 citation statements)

References 68 publications

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“…Preparation of antiserum directed against RAGE Antiserum directed against human RAGE for neutralising assays was prepared as described previously [6].…”

Section: Methodsmentioning

confidence: 99%

Telmisartan inhibits AGE-induced C-reactive protein production through downregulation of the receptor for AGE via peroxisome proliferator-activated receptor-gamma activation

et al. 2006

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Aims/hypothesis C-reactive protein (CRP), an acute-phase reactant produced mainly by the liver, is elevated in diabetes, thus contributing to the development and progression of atherosclerosis. However, the molecular mechanism underlying the elevation of CRP in diabetes is not fully understood. Since a crosstalk between AGE and angiotensin II (Ang II) has been proposed in the pathogenesis of accelerated atherosclerosis in diabetes, we examined here whether and how telmisartan, a unique Ang II type 1 receptor blocker (ARB) with peroxisome proliferatoractivated receptor-γ (PPAR-γ)-modulating activity, could inhibit AGE-induced CRP expression in a human hepatoma cell line, Hep3B cells. Methods Protein levels of the receptor for AGE (RAGE) were analysed by western blots. Gene expression was analysed by quantitative real-time RT-PCR. CRP released into the medium was measured with ELISA.

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“…Preparation of antiserum directed against RAGE Antiserum directed against human RAGE for neutralising assays was prepared as described previously [6].…”

Section: Methodsmentioning

confidence: 99%

Telmisartan inhibits AGE-induced C-reactive protein production through downregulation of the receptor for AGE via peroxisome proliferator-activated receptor-gamma activation

et al. 2006

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“…Intracellular ROS Production-Intracellular ROS production by human RPE cells in response to TNF-α, IL-1β, or IFN-γ treatment was measured by a cell-based fluorometric assay based on deacetylation and oxidation of non-fluorescent reduced CM-H 2 DCFDA (Molecular Probes) into fluorescent CM-DCF. The reliability and specificity of the probe have been established in various cells including cultured human RPE cells (Deshpande et al, 2000;Nishikawa et al, 2000;Touyz et al, 2001;Yamagishi et al, 2001;Higgins et al, 2003;Li et al, 2003;Fukami et al, 2004;Hermann et al, 2004;Hwang et al, 2004;Kannan et al, 2004;Shanker et al, 2004;Kim et al, 2005). RPE cells were seeded into 96-well plates pre-coated with poly-D-lysine (Sigma-Aldrich) and cultured for 1 day or 7days.…”

Section: Measurement Of Reactive Oxygen Species Production By Rpe Cellsmentioning

confidence: 99%

Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells

Yang

Elner

Bian

et al. 2007

Experimental Eye Research

365

242

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Reactive oxygen species (ROS) generated during inflammation are believed to play critical roles in various ocular diseases. However, the underlying mechanisms remain poorly understood. We investigated if pro-inflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin-1β (IL-1β), and interferon-γ (IFN-γ), induce ROS in human retinal pigment epithelial (RPE) cells. TNF-α, IL-1β and IFN-γ increased both intracellular and extracellular ROS production in a time-and dosedependent manner. Thenoyltrifluoroacetone (TTFA), an inhibitor of mitochondrial respiratory chain, blocked TNF-α-and IFN-γ-, but not IL-1β-induced ROS, whereas other two mitochondrial respiratory chain inhibitors, rotenone and antimycin A, had no effect. NADPH oxidase inhibitor (diphenylene iodinium) abolished the ROS production induced by IL-1β or IFN-γ, but not by TNF-α, whereas 6-aminonicotinamide (6AN), an inhibitor of the hexose monophosphate shunt (HMS), had no significant effects on the ROS induced by all three cytokines. ROS scavengers, pyrrolidinedithiocarbamate (PDTC) and N-acetyl-cysteine (NAC), reduced the levels of ROS induced by TNF-α, IL-1β and IFN-γ (P < 0.05). Collectively, these results demonstrate that TNF-α, IL-1β and IFN-γ increase mitochondrial-and NADPH oxidase-generated ROS in human RPE cells.

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“…AGE and TGF-b products have been implicated in the pathogenesis of human diabetic nephropathy [14,15]. Recently, we reported that KK-A y mice exhibited type 2 diabetes and diabetic nephropathy from 8 to 20 weeks of age [11].…”

Section: Discussionmentioning

confidence: 99%

Podocyte loss and albuminuria of KK-Ay mouse: A spontaneous animal model for human type 2 diabetic nephropathy

Ishikawa¹,

Ito²,

Tanimoto³

et al. 2012

JDM

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Podocyte loss was well known in type 2 diabetic nephropathy patients. The objective of the present study was to determine the number of podocytes and the degree of albuminuria in diabetic KK-A y /Ta (KK-A y ) mice which had been reported as diabetic nephropathy model. Diabetic KK-A y mice, diabetic KK/Ta mice and nondiabetic BALB/cA Jcl (BALB/cA) mice were studied. We analyzed glomerular lesions in all mice by morphometric analysis and immunofluorescence to determine the number of podocytes. Level of urinary albumin was also measured. Glomerular enlargement and mesangial expansion were observed in KK-A y mice. Mean number of podocytes per glomerulus (NG pod) in diabetic KK-A y mice was significantly lower than that in non-diabetic BALB/cA mice. Mean NG pod/glomerular area (GA) per glomerulus was also significantly decreased in diabetic KK-A y mice. The level of urinary albumin/creatinine ratio (ACR) in diabetic KK-A y mice was significantly higher than that in non-diabetic BALB/cA mice. These data suggest that podocyte loss might induce albuminuria in KK-A y mice. This finding confirmed our previous report that KK-A y mice, especially in terms of histological findings, are a suitable animal model for glomerular injury in type 2 diabetic nephropathy.

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AGEs activate mesangial TGF-β–Smad signaling via an angiotensin II type I receptor interaction

Cited by 210 publications

References 68 publications

Telmisartan inhibits AGE-induced C-reactive protein production through downregulation of the receptor for AGE via peroxisome proliferator-activated receptor-gamma activation

Telmisartan inhibits AGE-induced C-reactive protein production through downregulation of the receptor for AGE via peroxisome proliferator-activated receptor-gamma activation

Pro-inflammatory cytokines increase reactive oxygen species through mitochondria and NADPH oxidase in cultured RPE cells

Podocyte loss and albuminuria of KK-Ay mouse: A spontaneous animal model for human type 2 diabetic nephropathy

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