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Soluble Receptor for Advanced Glycation End Products Alleviates Nephritis in (NZB/NZW)F1 Mice

Title
 Soluble Receptor for Advanced Glycation End Products Alleviates Nephritis in (NZB/NZW)F1 Mice 
Authors
 Sang-Won Lee ; Kyu-Hyung Park ; Yong-Beom Park ; Donghoon Choi ; Soo-Kon Lee ; Sung-Yu Hong ; Ji-Hye Kim ; Sungha Park 
Issue Date
2013
Journal Title
 Arthritis and Rheumatism 
ISSN
 0004-3591 
Citation
 Arthritis and Rheumatism, Vol.65(7) : 1902~1912, 2013 
Abstract
OBJECTIVE: To investigate the efficacy of different doses of the soluble form of the receptor for advanced glycation end products (sRAGE) (conjugated to the Fc portion of immunoglobulin) in the treatment of nephritis in lupus-prone mice, in comparison with the efficacy of combination therapy with mycophenolate mofetil plus prednisolone. METHODS: Twenty-eight female (NZB/NZW)F1 mice were divided into 5 groups (untreated, sRAGE [dose groups of 0.5, 1, or 2 μg], or mycophenolate mofetil plus prednisolone). Proteinuria and histologic damage were evaluated. Immune complex deposition and the nuclear translocation of NF-κB in the kidney tissue were assessed by immunofluorescence staining. Serum concentrations of anti-double-stranded DNA (anti-dsDNA) and IgG subclasses were also measured. The population of T cells was evaluated using a fluorescence-activated cell sorter, and expression of intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 in the kidney tissue was assessed by immunohistochemical staining. RESULTS: In comparison with untreated mice, mice treated with 1 or 2 μg sRAGE showed significantly reduced proteinuria and attenuated histologic renal damage, with efficacy comparable to that of combination therapy. Treatment with 2 μg sRAGE significantly reduced immune complex deposition and decreased the serum concentrations of anti-dsDNA, IgG2a, IgG2b, and IgG3. In addition, sRAGE interrupted the nuclear translocation of NF-κB in the kidney, resulting in reduction in the expression of downstream genes of NF-κB in vivo and in vitro. Furthermore, sRAGE effectively modified T cell populations. CONCLUSION: Treatment with sRAGE significantly improved nephritis in lupus-prone mice, with efficacy comparable to that of standard induction treatment for lupus nephritis. These data suggest that sRAGE has antiinflammatory effects on the pathophysiology of lupus nephritis and could serve as a potent new therapy for this disease.
URI
http://ir.ymlib.yonsei.ac.kr/handle/22282913/87543
DOI
10.1002/art.37955
Appears in Collections:
1. 연구논문 > 1. College of Medicine > Dept. of Internal Medicine
1. 연구논문 > 1. College of Medicine > Yonsei Biomedical Research Center
1. 연구논문 > 5. Research Institutes > Cardiovascular Product Evaluation Center
Yonsei Authors
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Link
 http://onlinelibrary.wiley.com/doi/10.1002/art.37955/abstract
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