Inhibition of Diabetic Leukostasis and Blood-Retinal Barrier Breakdown with a Soluble Form of a Receptor for Advanced Glycation End Products

2007 ◽  
Vol 48 (2) ◽  
pp. 858 ◽  
Author(s):  
Yuichi Kaji ◽  
Tomohiko Usui ◽  
Susumu Ishida ◽  
Kenji Yamashiro ◽  
Tara C. B. Moore ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Soluble Form ◽  
Advanced Glycation ◽  
Blood Retinal Barrier ◽  
Glycation End Products ◽  
End Products ◽  
Barrier Breakdown

Receptor for advanced glycation end-products (RAGE) - soluble form (sRAGE) and gene polymorphisms in patients with breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21113-21113
Author(s):  
P. Tesarova ◽  
M. Kalousova ◽  
M. Jachymova ◽  
O. Mestek ◽  
L. Petruzelka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptors ◽  
Advanced Glycation End Products ◽  
Gene Polymorphisms ◽  
Soluble Form ◽  
Healthy Controls ◽  
Serum Concentrations ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products

21113 Background: Receptor for advanced glycation end products (RAGE) may be involved in the pathogenesis of the cancer progression and metastasis. Pathological effects mediated via RAGE are physiologically inhibited by soluble RAGE (sRAGE), so the higher sRAGE levels may confer the patients with cancer with better outcome.. Our aim was to study sRAGE and RAGE gene polymorphisms in patients with breast cancer. Methods: We studied sRAGE and RAGE polymorphisms in 120 patients with breast cancer (subdivided based on the clinical stage, histologic grading, expression of hormonal and C-erb B2 receptors) and in 92 healthy controls. Results: Despite higher serum concentrations of AGEs, serum concentrations of sRAGE were lower in patients with breast cancer compared to healthy controls (1581 ± 777 vs. 1803 ± 632 ng/ml, p < 0.05). Serum levels of sRAGE were higher in patients with advanced breast cancer (stage III), lower grade and positive estrogen receptors and intermediate positivity of C-erb B2 (Her-neu) receptors and were also influenced genetically (G82S and 2184 AG polymorphisms of the RAGE gene). Conclusions: Decreased sRAGE levels in patients with breast cancer may contribute to the progression of the disease. Patients with better outcome (with low grade and positive estrogen receptors) have higher sRAGE levels. Progression of the disease, may, however, increase sRAGE levels, possibly as a compensatory mechanism to counteract further progression. No significant financial relationships to disclose.

Independent determinants of soluble form of receptor for advanced glycation end products in elderly hypertensive patients

Metabolism ◽  
2009 ◽  
Vol 58 (3) ◽  
pp. 421-425 ◽  
Author(s):  
Kazuo Nakamura ◽  
Hisashi Adachi ◽  
Takanori Matsui ◽  
Yayoi Kurita ◽  
Masayoshi Takeuchi ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Soluble Form ◽  
Advanced Glycation ◽  
Hypertensive Patients ◽  
Glycation End Products ◽  
End Products ◽  
Elderly Hypertensive ◽  
Elderly Hypertensive Patients

Monocyte CD147 is induced by advanced glycation end products and high glucose concentration: possible role in diabetic complications

2010 ◽  
Vol 299 (5) ◽  
pp. C1212-C1219 ◽  
Author(s):  
W. Bao ◽  
D. Min ◽  
S. M. Twigg ◽  
N. A. Shackel ◽  
F. J. Warner ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Diabetic Complications ◽  
High Glucose ◽  
Transmembrane Protein ◽  
Soluble Form ◽  
Dependent Manner ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Cd147 Expression

CD147 is a highly glycosylated transmembrane protein that is known to play a role in regulation of many protein families. It has the unique ability to maintain functional activity in both the membrane bound state and in the soluble form. CD147 is known to play a role in regulation of matrix metalloproteinase (MMP) expression, but whether its expression is affected by the diabetic milieu is not known, and its role in regulation of monocyte MMPs in this environment has not been investigated. Therefore, in this study we investigated the effect of advanced glycation end products (AGEs) and high glucose (HG; 25 mM), on monocyte CD147 expression. Culture of THP-1 monocytes in the presence of AGEs or HG significantly increased CD147 at the gene and protein level. THP-1 cell results were confirmed using freshly isolated monocytes from human volunteers. The effect of AGEs and HG on CD147 expression was also mimicked by addition of proinflammatory cytokines. Addition of AGEs or HG also increased expression of monocyte MMP-1 and MMP-9 but not MMP-2. This increase in MMPs was significantly attenuated by inhibition of CD147 using either a small interfering RNA or an anti-CD147 antibody. Inhibition of NF-κB or addition of antibodies to either TNF-α or the receptor for AGE (RAGE) each significantly prevented in a dose-dependent manner the induction of CD147 gene and protein by AGE and also decreased MMP-1 and MMP-9. This novel result shows that AGEs can induce monocyte CD147 expression, an effect mediated by inflammatory pathways and RAGE. Because MMPs play a role in monocyte migration, inhibition of their regulator CD147 may assist in the prevention of diabetic complications, particularly those where monocyte infiltration is an early initiating event.

Elevated endogenous secretory receptor for advanced glycation end products (esRAGE) levels are associated with circulating soluble RAGE levels in diabetic children

2017 ◽  
Vol 30 (1) ◽  
Author(s):  
Reiko Saito ◽  
Shunsuke Araki ◽  
Yukiyo Yamamoto ◽  
Koichi Kusuhara
Keyword(s):  
Advanced Glycation End Products ◽  
Vascular Complications ◽  
Soluble Form ◽  
Advanced Glycation ◽  
Diabetic Vascular Complications ◽  
Soluble Rage ◽  
Control Serum ◽  
Glycation End Products ◽  
End Products ◽  
Diabetic Children

AbstractBackground:Advanced glycation end products (AGEs) and the receptor for AGE (RAGE) play an important role in the development of diabetic vascular complications. This study aimed at investigating the relationship between the soluble form of RAGE (sRAGE), endogenous secretory RAGE (esRAGE), and pentosidine in childhood diabetes.Methods:The study included 18 children with type 1 diabetes mellitus (T1DM), 10 with type 2 DM (T2DM), and 22 age-matched, non-diabetic children (control).Results:Serum sRAGE levels in the T1DM (2557.7 pg/mL) were significantly higher than both T2DM (1956.4 pg/mL) and control (1658.5 pg/mL). The circulating levels of esRAGE in T1DM and T2DM children were similar, but significantly higher than those of control. Serum pentosidine levels in the T1DM group were positively correlated with serum sRAGE and esRAGE levels, but not with anthropometric or biochemical measurements. The duration of diabetes and esRAGE levels were independent predictors of the circulating sRAGE levels.Conclusions:Unlike adults, children with diabetes exhibit high circulating esRAGE levels, and both sRAGE and esRAGE levels are correlated with pentosidine levels. These results suggest that circulating sRAGE and esRAGE in children may be surrogate markers for progressive glucose toxicity in pediatric patients with childhood-onset diabetes.

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