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

Authors
 Sang-Won Lee  ;  Kyu-Hyung Park  ;  Sungha Park  ;  Ji-Hye Kim  ;  Sung-Yu Hong  ;  Soo-Kon Lee  ;  Donghoon Choi  ;  Yong-Beom Park 
Citation
 Arthritis & Rheumatism, Vol.65(7) : 1902-1912, 2013 
Journal Title
 Arthritis & Rheumatism 
ISSN
 0004-3591 
Issue Date
2013
MeSH
Animals ; Anti-Inflammatory Agents/therapeutic use* ; Antigen-Antibody Complex/metabolism ; Disease Models, Animal ; Drug Therapy, Combination ; Female ; Kidney/metabolism ; Kidney/pathology ; Lupus Nephritis/pathology ; Lupus Nephritis/therapy* ; Mice ; Mice, Inbred NZB ; Mycophenolic Acid/analogs & derivatives ; Mycophenolic Acid/therapeutic use ; NF-kappa B ; Prednisolone/therapeutic use ; Proteinuria ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic/therapeutic use* ; Treatment Outcome
Keywords
Animals ; Anti-Inflammatory Agents/therapeutic use* ; Antigen-Antibody Complex/metabolism ; Disease Models, Animal ; Drug Therapy, Combination ; Female ; Kidney/metabolism ; Kidney/pathology ; Lupus Nephritis/pathology ; Lupus Nephritis/therapy* ; Mice ; Mice, Inbred NZB ; Mycophenolic Acid/analogs & derivatives ; Mycophenolic Acid/therapeutic use ; NF-kappa B ; Prednisolone/therapeutic use ; Proteinuria ; Receptor for Advanced Glycation End Products ; Receptors, Immunologic/therapeutic use* ; Treatment Outcome
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.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/art.37955/abstract
DOI
10.1002/art.37955
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
5. Research Institutes (연구소) > Cardiovascular Product Evaluation Center (심혈관제품유효성평가센터) > 1. Journal Papers
Yonsei Authors
Kim, Ji Hye(김지혜)
Park, Kyu Hyung(박규형)
Park, Sung Ha(박성하) ORCID logo https://orcid.org/0000-0001-5362-478X
Park, Yong Beom(박용범)
Lee, Sang Won(이상원) ORCID logo https://orcid.org/0000-0002-8038-3341
Lee, Soo Kon(이수곤)
Choi, Dong Hoon(최동훈) ORCID logo https://orcid.org/0000-0002-2009-9760
Hong, Sung Yu(홍성유)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/87543
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