Skip to main content

Advertisement

SpringerLink
Log in

Mycophenolic acid reverses IgA1 aberrant glycosylation through up-regulating Cosmc expression in IgA nephropathy

  • Nephrology - Original Paper
  • Published:
International Urology and Nephrology Aims and scope Submit manuscript

Abstract

Objective

Impaired core I β3-Gal-T-specific molecular chaperone (Cosmc) expression-caused IgA1 aberrant O-glycosylation is one of the main pathogeneses of IgA nephropathy (IgAN).This study tried to elucidate whether mycophenolic acid (MPA) could up-regulate Cosmc expression of peripheral lymphocytes in IgAN patients and reverse the dys-O-glycosylation.

Method

Peripheral lymphocytes of eighteen IgAN patients and twelve normal controls were isolated and cultured for 3–7 days with or without lipopolysaccharide (LPS) and MPA. Cosmc mRNA and protein expression levels were measured by real-time RT-PCR and western blot. IgA1 and O-glycosylation level were determined by enzyme-linked immunosorbent assay (ELISA) and VV lectin-binding test. Correlation analysis was performed between Cosmc expression levels and IgA1 O-glycosylation level.

Results

Cosmc mRNA expression and IgA1 O-glycosylation level in IgAN patients were significantly lower than normal controls. Treatment of LPS could obviously inhibit the Cosmc expression and increase the IgA1 secretion in peripheral lymphocytes of IgAN patients, which resulted in a significantly increase in IgA1 aberrant glycosylation level. Addition of MPA could significantly increase the Cosmc expression level along with a decrease in IgA1 secretion, leading to a reverse of aberrant glycosylation. A significant positive correlation between the Cosmc expression and IgA1 O-glycosylation level was noticed.

Conclusion

MPA can up-regulate the Cosmc expression and reverse the IgA1 aberrant O-glycosylation level in peripheral lymphocytes of IgAN patients, which might be the underlying mechanism of mycophenolate mofetil (MMF) therapy used in treating IgAN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Barratt J, Feehally J (2005) IgA nephropathy. J Am Soc Nephrol 16(7):2088–2097

    Article  PubMed  CAS  Google Scholar 

  2. Giannakakis K, Feriozzi S, Perez M et al (2007) Aberrantly glycosylated IgA1 in glomerular immune deposits of IgA nephropathy. J Am Soc Nephrol 18(12):3139–3146

    Article  PubMed  CAS  Google Scholar 

  3. Narita I, Gejyo F (2008) Pathogenetic significance of aberrant glycosylation of IgA1 in IgA nephropathy. Clin Exp Nephrol 12(5):332–338

    Article  PubMed  CAS  Google Scholar 

  4. Allen AC, Topham PS, Harper SJ et al (1997) Leucocyte beta 1,3 galactosyltransferase activity in IgA nephropathy. Nephrol Dial Transplant 12(4):701–706

    Article  PubMed  CAS  Google Scholar 

  5. Qin W, Zhou Q, Yang LC et al (2005) Peripheral B lymphocyte beta1, 3-galactosyltransferase and chaperone expression in immunoglobulin A nephropathy. J Intern Med 258(5):467–477

    Article  PubMed  CAS  Google Scholar 

  6. Qin W, Zhong X, Fan JM et al (2008) External suppression causes the low expression of the Cosmc gene in IgA nephropathy. Nephrol Dial Transplant 23(5):1608–1614

    Article  PubMed  CAS  Google Scholar 

  7. Xie LS, Qin W, Fan JM et al (2011) The role of C1GALT1C1 in lipopolysaccharide-induced IgA1 aberrant O-glycosylation in IgA nephropathy. Clin Invest Med 33(1):E5–E13

    Google Scholar 

  8. Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45

    Article  PubMed  CAS  Google Scholar 

  9. Moriyama T, Nakayama K, Iwasaki C et al (2012) Severity of nephrotic IgA nephropathy according to the Oxford classification. Int Urol Nephrol 44(4):1177–1184

    Article  PubMed  Google Scholar 

  10. Zhu C, Mertens PR (2012) IgA nephropathy and oxidative stress: news on clinically evaluated biomarkers hits the stage. Int Urol Nephrol 44(4):1277–1280

    Article  PubMed  Google Scholar 

  11. Xu LX, Zhao MH (2005) Aberrantly glycosylated serum IgA1 are closely associated with pathologic phenotypes of IgA nephropathy. Kidney Int 68(1):167–172

    Article  PubMed  CAS  Google Scholar 

  12. Ju T, Cummings RD (2002) A unique molecular chaperone Cosmc required for activity of the mammalian core 1 beta 3-galactosyltransferase. Proc Natl Acad Sci USA 99(26):16613–16618

    Article  PubMed  CAS  Google Scholar 

  13. Felner KM, Dinter A, Cartron JP et al (1998) Repressed beta-1,3-galactosyltransferase in the Tn syndrome. Biochim Biophys Acta 1406(1):115–125

    Article  PubMed  CAS  Google Scholar 

  14. Tang SC, Tang AW, Wong SS et al (2010) Long-term study of mycophenolate mofetil treatment in IgA nephropathy. Kidney Int. 77(6): 543–549

    Google Scholar 

  15. Tang S, Leung JC, Chan LY et al (2005) Mycophenolate mofetil alleviates persistent proteinuria in IgA nephropathy. Kidney Int 68(2):802–812

    Article  PubMed  CAS  Google Scholar 

  16. Xu G, Tu W, Jiang D et al (2009) Mycophenolate mofetil treatment for IgA nephropathy: a meta-analysis. Am J Nephrol 29(5):362–367

    Article  PubMed  CAS  Google Scholar 

  17. Allison AC (2005) Mechanisms of action of mycophenolate mofetil. Lupus 14(Suppl 1):s2–s8

    Article  PubMed  CAS  Google Scholar 

  18. Inoue TH, Sugiyama M, Kitagawa et al (2011) Abnormalities of glycogenes in tonsillar lymphocytes in IgA nephropathy. Adv Otorhinolaryngol 72:71–74

Download references

Acknowledgments

Our sincere thanks go to Professor Zhangxue Hu, Baihai Su and all the staff of Nephrology Division for their help. This work was supported by National Natural Science Foundation of China (No. 30800527 and 81270793).

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Nephrology, West China Hospital of Sichuan University, 37# Guoxue Road, Wuhou District, Chengdu, 610041, Sichuan, China

    Linshen Xie, Junming Fan, Ping Fu, Yi Tang, Ye Tao & Wei Qin

  2. Department of Medicine, Division of Clinical Rheumatology, West China Hospital of Sichuan University, Chengdu, Sichuan, China

    Chunyu Tan

  3. State Key Laboratory of Biotherapy of Sichuan University, Chengdu, Sichuan, China

    Junming Fan

Authors
  1. Linshen Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chunyu Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Junming Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ping Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yi Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ye Tao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Qin.

Additional information

Linshen Xie and Chunyu Tan have been equally contributed to this paper.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xie, L., Tan, C., Fan, J. et al. Mycophenolic acid reverses IgA1 aberrant glycosylation through up-regulating Cosmc expression in IgA nephropathy. Int Urol Nephrol 45, 571–579 (2013). https://doi.org/10.1007/s11255-012-0313-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11255-012-0313-y

Keywords

Search

Navigation