Skip to main content
SpringerLink
Log in

MicroRNA-326 contributes to autoimmune thyroiditis by targeting the Ets-1 protein

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

Purpose:

MicroRNA-326 (miR-326), as a member of the microRNA (miRNA) family, which includes endogenous single-stranded, conserved, noncoding small RNAs, has been reported to play important roles in autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus. However, few studies of the role of miR-326 in autoimmune thyroiditis (AIT) have been published. Here, we explored the roles of miR-326 and the involved pathway in iodine-induced AIT.

Methods:

NOD.H-2h4 mice, which are a model of human AIT, were randomly divided into a normal water control group and a high-iodine group. Mice in the high-iodine group were administered 0.05% NaI (~1000 times the normal daily iodine intake), and mice in the control group received sterile water. Furthermore, we evaluated small interfering RNA (siRNA) interference in spleen mononuclear cell experiments in vitro.

Results:

In this study, we found that Th17 cells were significantly increased with a high expression of miR-326 in an iodine-induced thyroiditis NOD.H-2h4 mouse model. In addition, the expression of Ets-1 protein, a negative regulator of Th17 differentiation, was significantly decreased. Intriguingly, our analysis showed that Ets-1 protein expression was negatively correlated with miR-326 levels in AIT mice (r = −0.814, p < 0.01). Our study indicated that miR-326 inhibited Ets-1 protein expression and promoted the differentiation of Th17 cells during the onset and development of AIT. The addition of a miR-326 inhibitor reversed Th17 cell production and Ets-1 protein expression, supporting this hypothesis.

Conclusions:

The results of our study suggest that miR-326 may target the Ets-1 protein to contribute to iodide-induced thyroiditis, providing a new theoretical basis for the use of miRNA targeting therapy for the treatment of autoimmune diseases.

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

Similar content being viewed by others

References

  1. P. Caturegli, A. De Remigis, N.R. Rose, Hashimoto thyroiditis: clinical and diagnostic criteria. Autoimmun. Rev. 13(4-5), 391–397 (2014).

    Article  CAS  PubMed  Google Scholar 

  2. P. Fallahi et al. The association of other autoimmune diseases in patients with autoimmune thyroiditis: review of the literature and report of a large series of patients. Autoimmun. Rev. 15(12), 1125–1128 (2016)

    Article  CAS  PubMed  Google Scholar 

  3. K. Boelaert et al. Prevalence and relative risk of other autoimmune diseases in subjects with autoimmune thyroid disease. Am. J. Med. 123(2), 183– e1-9 (2010)

    Article  PubMed  Google Scholar 

  4. H. Braley-Mullen et al. Spontaneous autoimmune thyroiditis in NOD.H-2h4 mice. J. Autoimmun. 12(3), 157–165 (1999)

    Article  CAS  PubMed  Google Scholar 

  5. K. Zaletel, S. Gaberscek, Hashimoto’s thyroiditis: from genes to the disease. Curr. Genomics 12(8), 576–588 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. C. Du et al. MicroRNA miR-326 regulates TH-17 differentiation and is associated with the pathogenesis of multiple sclerosis. Nat. Immunol. 10(12), 1252–1259 (2009)

    Article  CAS  PubMed  Google Scholar 

  7. J.A. Emamaullee et al. Inhibition of Th17 cells regulates autoimmune diabetes in NOD mice. Diabetes 58(6), 1302–1311 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. C.R. Li, E.E. Mueller, L.M. Bradley, Islet antigen-specific Th17 cells can induce TNF-alpha-dependent autoimmune diabetes. J. Immunol. 192(4), 1425–1432 (2014)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. R. Kugyelka et al. Enigma of IL-17 and Th17 cells in rheumatoid arthritis and in autoimmune animal models of arthritis. Mediators Inflamm. 2016, 6145810 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  10. A.J. Martin, L. Zhou, S.D. Miller, MicroRNA--managing the TH-17 inflammatory response. Nat. Immunol. 10(12), 1229–1231 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. E. Bettelli et al. Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441(7090), 235–238 (2006)

    Article  CAS  PubMed  Google Scholar 

  12. C. Dong, TH17 cells in development: an updated view of their molecular identity and genetic programming. Nat. Rev. Immunol. 8(5), 337–348 (2008)

    Article  CAS  PubMed  Google Scholar 

  13. J. Moisan et al. Ets-1 is a negative regulator of Th17 differentiation. J. Exp. Med. 204(12), 2825–2835 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. C.P. Petersen et al. Short RNAs repress translation after initiation in mammalian cells. Mol. Cell 21(4), 533–542 (2006)

    Article  CAS  PubMed  Google Scholar 

  15. R. Thermann, M.W. Hentze, Drosophila miR2 induces pseudo-polysomes and inhibits translation initiation. Nature 447(7146), 875–878 (2007)

    Article  CAS  PubMed  Google Scholar 

  16. M.D. Ballantyne, R.A. McDonald, A.H. Baker, lncRNA/MicroRNA interactions in the vasculature. Clin. Pharmacol. Ther. 99(5), 494–501 (2016)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. R.M. O’Connell et al. Physiological and pathological roles for microRNAs in the immune system. Nat. Rev. Immunol. 10(2), 111–122 (2010)

    Article  PubMed  Google Scholar 

  18. Y. Zheng, Z. Wang, Z. Zhou, miRNAs: novel regulators of autoimmunity-mediated pancreatic beta-cell destruction in type 1 diabetes. Cell. Mol. Immunol. 14(6), 488–496 (2017)

  19. L.P. Garo, G. Murugaiyan, Contribution of MicroRNAs to autoimmune diseases. Cell Mol. Life Sci. 73(10), 2041–2051 (2016)

    Article  CAS  PubMed  Google Scholar 

  20. G. Sebastiani et al. Increased expression of microRNA miR-326 in type 1 diabetic patients with ongoing islet autoimmunity. Diabetes Metab. Res. Rev. 27(8), 862–866 (2011)

    Article  CAS  PubMed  Google Scholar 

  21. M.A. Honardoost et al. miR-326 and miR-26a, two potential markers for diagnosis of relapse and remission phases in patient with relapsing-remitting multiple sclerosis. Gene 544(2), 128–133 (2014)

    Article  CAS  PubMed  Google Scholar 

  22. G. Murugaiyan et al. Silencing microRNA-155 ameliorates experimental autoimmune encephalomyelitis. J. Immunol. 187(5), 2213–2221 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. X.G. Sun et al. Negative correlation between miR-326 and Ets-1 in regulatory T cells from new-onset SLE patients. Inflammation 39(2), 822–829 (2016)

    Article  CAS  PubMed  Google Scholar 

  24. P.L. Podolin et al. I-E+ nonobese diabetic mice develop insulitis and diabetes. J. Exp. Med. 178(3), 793–803 (1993)

    Article  CAS  PubMed  Google Scholar 

  25. A.O. Vladutiu, N.R. Rose, Autoimmune murine thyroiditis relation to histocompatibility (H-2) type. Science 174(4014), 1137–1139 (1971)

    Article  CAS  PubMed  Google Scholar 

  26. H. Braley-Mullen, S. Yu, NOD.H-2h4 mice: an important and underutilized animal model of autoimmune thyroiditis and Sjogren’s syndrome. Adv. Immunol. 126, 1–43 (2015)

    Article  PubMed  Google Scholar 

  27. Y. Nagayama et al. CD4+CD25+naturally occurring regulatory T cells and not lymphopenia play a role in the pathogenesis of iodide-induced autoimmune thyroiditis in NOD-H2h4 mice. J. Autoimmun. 29(2-3), 195–202 (2007)

    Article  CAS  PubMed  Google Scholar 

  28. I. Horie et al. T helper type 17 immune response plays an indispensable role for development of iodine-induced autoimmune thyroiditis in nonobese diabetic-H2h4 mice. Endocrinology 150(11), 5135–5142 (2009)

    Article  CAS  PubMed  Google Scholar 

  29. X. Teng et al. Experimental study on the effects of chronic iodine excess on thyroid function, structure, and autoimmunity in autoimmune-prone NOD.H-2h4 mice. Clin. Exp. Med. 9(1), 51–59 (2009)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. H. Yamada et al. Circulating microRNAs in autoimmune thyroid diseases. Clin. Endocrinol. 81(2), 276–281 (2014)

    Article  CAS  Google Scholar 

  31. J. Zhu et al. MicroRNA-142-5p contributes to Hashimoto’s thyroiditis by targeting CLDN1. J. Transl. Med. 14(1), 166 (2016)

    Article  PubMed  PubMed Central  Google Scholar 

  32. C. Bernecker et al. MicroRNAs miR-146a1, miR-155_2, and miR-200a1 are regulated in autoimmune thyroid diseases. Thyroid 22(12), 1294–1295 (2012)

    Article  CAS  PubMed  Google Scholar 

  33. D. Li et al. Th17 cell plays a role in the pathogenesis of Hashimoto’s thyroiditis in patients. Clin. Immunol. 149(3), 411–420 (2013)

    Article  CAS  PubMed  Google Scholar 

  34. R.X. Leng et al. The dual nature of Ets-1: focus to the pathogenesis of systemic lupus erythematosus. Autoimmun. Rev. 10(8), 439–443 (2011)

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the Chinese National Natural Science Foundation (Grant no. 81471003).

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang, 110001, PR China

    Na Zhao, Hongjin Zou, Jing Qin, Chenling Fan, Yongping Liu, Shuo Wang, Zhongyan Shan, Weiping Teng & Yushu Li

Authors
  1. Na Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongjin Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chenling Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yongping Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shuo Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Zhongyan Shan
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Weiping Teng
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yushu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yushu Li.

Ethics declarations

Conflicts of interest

The authors declare that they have no competing interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, N., Zou, H., Qin, J. et al. MicroRNA-326 contributes to autoimmune thyroiditis by targeting the Ets-1 protein. Endocrine 59, 120–129 (2018). https://doi.org/10.1007/s12020-017-1465-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-017-1465-4

Keywords

Search

Navigation