title: TGF-β1 mimics the effect of IL-4 on the glycosylation of IgA1 by downregulating core 1 β1, 3-galactosyltransferase and Cosmc.
abstract: 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‑β1 (TGF‑β1) on the glycosylation of IgA1 and the associated mechanism. The mRNA levels of core1 β1, 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‑β1. The IgA1‑positive human B‑cell line was cultured with different concentrations of recombinant human TGF‑β1 (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‑β1 (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‑β1. TGF‑β1 stimulation significantly decreased the mRNA levels of C1GalT1 and Cosmc. TGF‑β1 may be key in controlling the glycosylation of IgA1, in part via the downregulation of C1GalT1 and Cosmc.
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xiao
authors.affiliation: Department of Nephrology, Affiliated Jiujiang Hospital of Nanchang University, Jiujiang, Jiangxi 332000, P.R. China.
authors.forename: Manting
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Microbiology, Jiangxi Academy of Sciences, Nanchang, Jiangxi 330096, P.R. China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Xiong
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Qiuyue
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Qinkai
authors.initials: Q
authors.lastname: Chen
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D005700:Galactosyltransferases / Q000235:genetics*; D005786:Gene Expression Regulation; D005922:Glomerulonephritis, IGA / Q000235:genetics / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007070:Immunoglobulin A / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism*; D018832:Molecular Chaperones / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012794:Sialic Acids / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: C505369:C1GALT1C1 protein, human; D007070:Immunoglobulin A; D018832:Molecular Chaperones; D012333:RNA, Messenger; D012794:Sialic Acids; D053773:Transforming Growth Factor beta1; D015847:Interleukin-4; C505293:C1GALT1 protein, human; D005700:Galactosyltransferases