| The role of C1GALT1C1 in lipopolysaccharide-induced IgA1 aberrant O-glycosylation in IgA nephropathy. | |
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MedLine Citation:
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PMID: 20144270 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: IgA1 aberrant O-glycosylation is one of the main pathogenetic features of IgA nephropathy (IgAN). This study attempted to determine the role of C1GALT1C1 in aberrant IgA1 O-glycosylation induced by lipopolysaccharide (LPS) and identify potential therapeutic targets in IgAN. METHODS: Lymphocytes isolated from 22 patients with IgAN and 17 normal controls were cultured for 3 to 7 days with or without LPS and 5-azacytidine (5-AZA). Expression levels of C1GALT1C1 mRNA and protein were measured by real-time PCR and Western blot analysis, respectively. Concentration of IgA1 and level of O-glycosylation were determined by ELISA and Vicia villosa (VV) lectin-binding assay. Correlation analysis was performed between the expression of C1GALT1C1 protein and IgA1 O-glycosylation. RESULTS: Lymphocytes from patients with IgAN secreted more IgA1 than that from normal controls after LPS stimulation (P=0.26, 0.002 and 0.005 on the 3rd, 5th and 7th day, respectively) which could be inhibited by 5-AZA (P=0.001, 0.025 and 0.001 on the 3rd, 5th and 7th day, respectively). Moreover, LPS stimulation could obviously inhibit C1GALT1C1 expression in patients with IgAN (decreased by 71%, 82% and 92% on the 3rd, 5th and 7th day, respectively; P < 0.001), and cause a significant decrease of IgA1 O-glycosylation compared with normal controls (P=0.004, 0.003 and 0.03 on the 3rd, 5th and 7th day, respectively). When 5-AZA was added, the level of C1GALT1C1 expression increased dramatically (1.98, 5.53 and 8.97 times on the 3rd, 5th and 7th day, respectively; P < 0.001) along with an increase of IgA1 O-glycosylation (P=0.295, 0.09 and 0.003 on the 3rd, 5th and 7th day, respectively). However, normal controls showed no significant change in C1GALT1C1 expression and IgA1 O-glycosylation after LPS stimulation (P > 0.05). CONCLUSION: LPS induced IgA1 aberrant O-glycosylation and suppressed C1GALT1C1 expression in patients with IgAN. Upregulation of C1GALT1C1 expression by 5-AZA could reverse the IgA1 aberrant O-glycosylation. These results suggest that C1GALT1C1 may play a key role in the regulation of IgA1 O-glycosylation. |
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Authors:
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Lin-Shen Xie; Wei Qin; Jun-Ming Fan; Jun Huang; Xi-Sheng Xie; Zi Li |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-02-01 |
Journal Detail:
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Title: Clinical and investigative medicine. M?decine clinique et experimentale Volume: 33 ISSN: 1488-2353 ISO Abbreviation: Clin Invest Med Publication Date: 2010 |
Date Detail:
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Created Date: 2010-02-10 Completed Date: 2010-04-22 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7804071 Medline TA: Clin Invest Med Country: Canada |
Other Details:
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Languages: eng Pagination: E5-13 Citation Subset: IM |
Affiliation:
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Department of Nephrology, West China Hospital of Sichuan University, Chengdu City, Sichuan Province, China. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adolescent Adult Azacitidine / metabolism Case-Control Studies Cells, Cultured Female Glomerulonephritis, IGA / immunology*, metabolism Glycosylation Humans Immunoglobulin A / immunology*, metabolism Lipopolysaccharides / metabolism Lymphocytes / metabolism Male Molecular Chaperones / genetics, metabolism* RNA, Messenger / metabolism Time Factors Up-Regulation / immunology Young Adult |
| Chemical | |
Reg. No./Substance:
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0/C1GALT1C1 protein, human; 0/Immunoglobulin A; 0/Lipopolysaccharides; 0/Molecular Chaperones; 0/RNA, Messenger; 320-67-2/Azacitidine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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