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

Xiao,Jun; Wang,Manting; Xiong,Dawei; Wang,Ying; Li,Qiuyue; Zhou,Jing; Chen,Qinkai

doi:10.3892/mmr.2016.6084

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

Authors:
- Jun Xiao
- Manting Wang
- Dawei Xiong
- Ying Wang
- Qiuyue Li
- Jing Zhou
- Qinkai Chen
View Affiliations

Affiliations: Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China, Department of Nephrology, Affiliated Jiujiang Hospital of Nanchang University, Jiujiang, Jiangxi 332000, P.R. China, Institute of Microbiology, Jiangxi Academy of Sciences, Nanchang, Jiangxi 330096, P.R. China
Published online on: December 29, 2016 https://doi.org/10.3892/mmr.2016.6084
Pages: 969-974

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

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.

View Figures

View References

1	D'Amico G: Natural history of idiopathic IgA nephropathy and factors predictive of disease outcome. Semin Nephrol. 24:179–196. 2004. View Article : Google Scholar : PubMed/NCBI
2	Barratt J, Feehally J and Smith AC: Pathogenesis of IgA nephropathy. Semin Nephrol. 24:197–217. 2004. View Article : Google Scholar : PubMed/NCBI
3	Tarelli E, Smith AC, Hendry BM, Challacombe SJ and Pouria S: Human serum IgA1 is substituted with up to six O-glycans as shown by matrix assisted laser desorption ionisation time-of-flight mass spectrometry. Carbohydr Res. 339:2329–2335. 2004. View Article : Google Scholar : PubMed/NCBI
4	Renfrow MB, Cooper HJ, Tomana M, Kulhavy R, Hiki Y, Toma K, Emmett MR, Mestecky J, Marshall AG and Novak J: Determination of aberrant O-glycosylation in the IgA1 hinge region by electron capture dissociation Fourier transform-ion cyclotron resonance mass spectrometry. J Biol Chem. 280:19136–19145. 2005. View Article : Google Scholar : PubMed/NCBI
5	Moldoveanu Z, Wyatt RJ, Lee JY, Tomana M, Julian BA, Mestecky J, Huang WQ, Anreddy SR, Hall S, Hastings MC, et al: Patients with IgA nephropathy have increased serum galactose-deficient IgA1 levels. Kidney Int. 71:1148–1154. 2007. View Article : Google Scholar : PubMed/NCBI
6	Kokubo T, Hiki Y, Iwase H, Horii A, Tanaka A, Nishikido J, Hotta K and Kobayashi Y: Evidence for involvement of IgA1 hinge glycopeptide in the IgA1-IgA1 interaction in IgA nephropathy. J Am Soc Nephrol. 8:915–919. 1997.PubMed/NCBI
7	Yan Y, Xu LX, Zhang JJ, Zhang Y and Zhao MH: Self-aggregated deglycosylated IgA1 with or without IgG were associated with the development of IgA nephropathy. Clin Exp Immunol. 144:17–24. 2006. View Article : Google Scholar : PubMed/NCBI
8	Barratt J, Smith AC and Feehally J: The pathogenic role of IgA1 O-linked glycosylation in the pathogenesis of IgA nephropathy. Nephrology. 12:275–284. 2007. View Article : Google Scholar : PubMed/NCBI
9	Floege J: The pathogenesis of IgA nephropathy: What is new and how does it change therapeutic approaches? Am J Kidney Dis. 58:992–1004. 2011. View Article : Google Scholar : PubMed/NCBI
10	Ju T, Brewer K, D'Souza A, Cummings RD and Canfield WM: Cloning and expression of human core 1 beta1,3-galactosyltransferase. J Biol Chem. 277:178–186. 2002. View Article : Google Scholar : PubMed/NCBI
11	Ju T and Cummings RD: A unique molecular chaperone Cosmc required for activity of the mammalian core 1 beta 3-galactosyltransferase. Proc Natl Acad Sci USA. 99:16613–16618. 2002. View Article : Google Scholar : PubMed/NCBI
12	Allen AC, Topham PS, Harper SJ and Feehally J: Leucocyte beta 1,3 galactosyltransferase activity in IgA nephropathy. Nephrol Dial Transplant. 12:701–706. 1997. View Article : Google Scholar : PubMed/NCBI
13	Suzuki H, Moldoveanu Z, Hall S, Brown R, Vu HL, Novak L, Julian BA, Tomana M, Wyatt RJ, Edberg JC, et al: IgA1-secreting cell lines from patients with IgA nephropathy produce aberrantly glycosylated IgA1. J Clin Invest. 118:629–639. 2008.PubMed/NCBI
14	Takahashi K, Raska M, Horynova M Stuchlova, Hall SD, Poulsen K, Kilian M, Hiki Y, Yuzawa Y, Moldoveanu Z, Julian BA, et al: Enzymatic sialylation of IgA1 O-Glycans: Implications for studies of IgA nephropathy. PLoS One. 9:e990262014. View Article : Google Scholar : PubMed/NCBI
15	Nagasawa R, Maruyama N, Imasawa T and Mitarai T: Role of T cells in murine IgA nephropathy. Nephrol Dial Transplant. 14 Suppl 1:S12–S13. 1999. View Article : Google Scholar
16	Lycke N: T cell and cytokine regulation of the IgA response. Chem Immunol. 71:209–234. 1998. View Article : Google Scholar : PubMed/NCBI
17	Chintalacharuvu SR and Emancipator SN: The glycosylation of IgA produced by murine B cells is altered by Th2 cytokines. J Immunol. 159:2327–2333. 1997.PubMed/NCBI
18	Yamada K, Kobayashi N, Ikeda T, Suzuki Y, Tsuge T, Horikoshi S, Emancipator SN and Tomino Y: Down-regulation of core 1 beta 1,3-galactosyltransferase and Cosmc by Th2 cytokine alters O-glycosylation of IgA1. Nephrol Dial Transplant. 25:3890–3897. 2010. View Article : Google Scholar : PubMed/NCBI
19	Suzuki H, Raska M, Yamada K, Moldoveanu Z, Julian BA, Wyatt RJ, Tomino Y, Gharavi AG and Novak J: Cytokines Alter IgA1 O-Glycosylation by Dysregulating C1GalT1 and ST6GalNAc-II Enzymes. J Biol Chem. 289:5330–5339. 2014. View Article : Google Scholar : PubMed/NCBI
20	Yu HH, Chu KH, Yang YH, Lee JH, Wang LC, Lin YT and Chiang BL: Genetics and Immunopathogenesis of IgA Nephropathy. Clinic Rev Allerg Immunol. 41:198–213. 2011. View Article : Google Scholar
21	Toyabe S, Harada W and Uchiyama M: Oligoclonally expanding gammadelta T lymphocytes induce IgA switching in IgA nephropathy. Clin Exp Immunol. 124:110–117. 2001. View Article : Google Scholar : PubMed/NCBI
22	Meng H, Zhang L, E XQ, Ye F, Li H, Han C, Yamakawa M and Jin X: Application of Oxford classification, and overexpression of transforming growth factor-β1 and immunoglobulins in immunoglobulin A nephropathy: Correlation with World Health Organization classification of immunoglobulin A nephropathy in a Chinese patient cohort. Transl Res. 163:8–18. 2014. View Article : Google Scholar : PubMed/NCBI
23	Yang YH, Huang MT, Lin SC, Lin YT, Tsai MJ and Chiang BL: Increased transfroming growth factor-beta (TGF-beta)-secreting T cells and IgA anti-cardiolipin antibody levels during acute stage of childhood Henoch-Schönlein purpura. Clin Exp Immunol. 122:285–290. 2000. View Article : Google Scholar : PubMed/NCBI
24	Xiao J, Cao CY, Zhou J and Wang WH: Changes in levels of Th1, Th2 and Th3 cells in peripheral blood in patients with IgA nephropathy and their significance. Prac Clin Med. 13:28–31. 2012.(In Chinese).
25	Qin W, Zhou Q, Yang LC, Li Z, Su BH, Luo H and Fan JM: Peripheral B lymphocyte beta1, 3-galactosyltransferase and chaperone expression in immunoglobulin A nephropathy. J Intern Med. 258:467–477. 2005. View Article : Google Scholar : PubMed/NCBI
26	Xie LS, Qin W, Fan JM, Huang J, Xie XS and Li Z: The role of C1GALT1C1 in lipopolysaccharide-induced IgA1 aberrant O-glycosylation in IgA nephropathy. Clin Invest Med. 33:E5–E13. 2010.PubMed/NCBI
27	De Wolff JF, Dickinson SJ, Smith AC, Molyneux K, Feehally J, Simon A and Barratt J: Abnormal IgD and IgA1 O-glycosylation in hyperimmunoglobulinaemia D and periodic fever syndrome. Clin Exp Med. 9:291–296. 2009. View Article : Google Scholar : PubMed/NCBI
28	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
29	Prud'homme GJ and Piccirillo CA: The inhibitory effects of transforming growth factor-beta-1(TGF-beta1) in autoimmune diseases. J Autoimmun. 14:23–42. 2000. View Article : Google Scholar : PubMed/NCBI
30	Del Prete D, Gambaro G, Lupo A, Anglani F, Brezzi B, Magistroni R, Graziotto R, Furci L, Modena F, Bernich P, et al: Precocious activation of genes of the renin-angiotensin system and the fibrogenic cascade in IgA glomerulonephritis. Kidney Int. 64:149–159. 2003. View Article : Google Scholar : PubMed/NCBI
31	Leung JC, Chan LY, Tsang AW, Liu EW, Lam MF, Tang SC and Lai KN: Anti-macrophagemigration inhibitory factor reduces transforming growth factor-beta 1 expression in experimental IgA nephropathy. Nephrol Dial Transplant. 19:1976–1985. 2004. View Article : Google Scholar : PubMed/NCBI
32	Zhong Q, Leung JC, Chan LY, Tsang AW, Chen X and Lai KN: The study of Chinese medicinal herbal formula Shen San Fang in the treatment of experimental IgA nephropathy. Am J Chin Med. 33:613–626. 2005. View Article : Google Scholar : PubMed/NCBI
33	Chihara Y, Ono H, Ishimitsu T, Ono Y, Ishikawa K, Rakugi H, Ogihara T and Matsuoka H: Roles of TGF-beta 1 and apoptosis in the progression of glomerulosclerosis in human IgA nephropathy. Clin Nephrol. 65:385–392. 2006. View Article : Google Scholar : PubMed/NCBI
34	Kim PH and Kagnoff MF: Transforming growth factor beta 1 increases IgA isotype switching at the clonal level. J Immunol. 145:3773–3778. 1990.PubMed/NCBI
35	Cazac BB and Roes J: TGF-beta receptor controls B cell responsiveness and induction of IgA in vivo. Immunity. 13:443–451. 2000. View Article : Google Scholar : PubMed/NCBI
36	Boratyńska M: Urine excretion of transforming growth factor-beta 1 in chronic allograft nephropathy. Ann Transplant. 4:23–28. 1999.
37	Ibelgaufts H: Cytokines and Cells Online Pathfinder Encyclopaedia (COPE). http://www.copewithcytokines.de/cope.cgi2007.
38	Kajdaniuk D, Marek B, Borgiel-Marek H and Kos-Kudła B: Transforming growth factor β1 (TGF-β1) in physiology and pathology. Endokrynol Pol. 64:384–396. 2013. View Article : Google Scholar : PubMed/NCBI
39	Barratt J and Feehally J: IgA nephropathy. J Am Soc Nephrol. 16:2088–2097. 2005. View Article : Google Scholar : PubMed/NCBI
40	Coppo R and Amore A: Aberrant glycosylation in IgA nephropathy (IgAN). Kidney Int. 65:1544–1547. 2004. View Article : Google Scholar : PubMed/NCBI
41	Julian BA and Novak J: IgA nephropathy: An update. Curr Opin Nephrol Hypertens. 13:171–179. 2004. View Article : Google Scholar : PubMed/NCBI
42	Lai KN: Pathogenesis of IgA nephropathy. Nat Rev Nephrol. 8:275–283. 2012. View Article : Google Scholar : PubMed/NCBI
43	Ju T, Brewer K, D'Souza A, Cummings RD and Canfield WM: Cloning and expression of human core 1 beta1, 3-galactosyltransferase. J Biol Chem. 277:178–186. 2002. View Article : Google Scholar : PubMed/NCBI
44	Serino G, Sallustio F, Cox SN, Pesce F and Schena FP: Abnormal miR-148b expression promotes aberrant glycosylation of IgA1 in IgA nephropathy. J Am Soc Nephrol. 23:814–824. 2012. View Article : Google Scholar : PubMed/NCBI
45	He L, Peng Y, Liu H, Yin W, Chen X, Peng X, Shao J, Liu Y and Liu F: Activation of the interleukin-4/signal transducer and activator of transcription 6 signaling pathway and homeodomain-interacting protein kinase 2 production by tonsillar mononuclear cells in IgA nephropathy. Am J Nephrol. 38:321–332. 2013. View Article : Google Scholar : PubMed/NCBI
46	Inoue T, Sugiyama H, Hiki Y, Takiue K, Morinaga H, Kitagawa M, Maeshima Y, Fukushima K, Nishizaki K, Akagi H, et al: Differential expression of glycogenes in tonsillar B lymphocytes in association with proteinuria and renal dysfunction in IgA nephropathy. Clin Immunol. 136:447–455. 2010. View Article : Google Scholar : PubMed/NCBI