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

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


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.

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). simplehttp://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

Related Articles

Journal Cover

February 2017
Volume 15 Issue 2

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Xiao, J., Wang, M., Xiong, D., Wang, Y., Li, Q., Zhou, J., & Chen, Q. (2017). TGF-β1 mimics the effect of IL-4 on the glycosylation of IgA1 by downregulating core 1 β1, 3-galactosyltransferase and Cosmc. Molecular Medicine Reports, 15, 969-974. https://doi.org/10.3892/mmr.2016.6084
MLA
Xiao, J., Wang, M., Xiong, D., Wang, Y., Li, Q., Zhou, J., Chen, Q."TGF-β1 mimics the effect of IL-4 on the glycosylation of IgA1 by downregulating core 1 β1, 3-galactosyltransferase and Cosmc". Molecular Medicine Reports 15.2 (2017): 969-974.
Chicago
Xiao, J., Wang, M., Xiong, D., Wang, Y., Li, Q., Zhou, J., Chen, Q."TGF-β1 mimics the effect of IL-4 on the glycosylation of IgA1 by downregulating core 1 β1, 3-galactosyltransferase and Cosmc". Molecular Medicine Reports 15, no. 2 (2017): 969-974. https://doi.org/10.3892/mmr.2016.6084