TGF-β1 mimics the effect of IL-4 on the glycosylation of IgA1 by downregulating core 1 β1, 3-galactosyltransferase and Cosmc

被引:17
作者
Xiao, Jun [1 ]
Wang, Manting [2 ]
Xiong, Dawei [3 ]
Wang, Ying [1 ]
Li, Qiuyue [1 ]
Zhou, Jing [1 ]
Chen, Qinkai [1 ]
机构
[1] Nanchang Univ, Affiliated Hosp 1, Dept Nephrol, 17 YongWai St, Nanchang 330006, Jiangxi, Peoples R China
[2] Nanchang Univ, Affiliated Jiujiang Hosp, Dept Nephrol, Jiujiang 332000, Jiangxi, Peoples R China
[3] Jiangxi Acad Sci, Inst Microbiol, Nanchang 330096, Jiangxi, Peoples R China
关键词
IgA nephropathy; transforming growth factor-beta 1; IgA1; glycosylation; core1; beta; 1; 3-galactosyltransferase; Cosmc; IMMUNOGLOBULIN-A NEPHROPATHY; ABERRANT O-GLYCOSYLATION; TRANSFORMING GROWTH-FACTOR-BETA-1; MASS-SPECTROMETRY; T-CELLS; PATHOGENESIS; EXPRESSION; BETA-1,3-GALACTOSYLTRANSFERASE; ACTIVATION; CYTOKINES;
D O I
10.3892/mmr.2016.6084
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The aberrant glycosylation of IgA1 is pivotal in the pathogenesis of IgA nephropathy (IgAN). The aim of the present study was to investigate the effect of transforming growth factor-beta 1 (TGF-beta 1) on the glycosylation of IgA1 and the associated mechanism. The mRNA levels of core1 beta 1, 3-galactosyltransferase (C1GalT1) and its molecular chaperone, Cosmc, were analyzed, as was the subsequent O-glycosylation of IgA1, in a human B-cell line stimulated with TGF-beta 1. The IgA1-positive human B-cell line was cultured with different concentrations of recombinant human TGF-beta 1 (5, 10, 15 and 30 ng/ml). The production and glycosylation of IgA1 were assayed using sandwich ELISA and enzyme-linked lectin binding assays, respectively, and the mRNA levels of C1GalT1 and Cosmc were quantified using reverse transcription-quantitative polymerase chain reaction analysis. The results showed that the production of IgA1 was stimulated by low concentrations of TGF-beta 1 (5 or 10 ng/ml) and was suppressed by high concentrations (15 or 30 ng/ml). The terminal glycosylation of secreted IgA1 was altered in response to TGF-beta 1. TGF-beta 1 stimulation significantly decreased the mRNA levels of C1GalT1 and Cosmc. TGF-beta 1 may be key in controlling the glycosylation of IgA1, in part via the downregulation of C1GalT1 and Cosmc.
引用
收藏
页码:969 / 974
页数:6
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