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MicroRNA expression profiles of the thyroid after goiter formation and involution in rats under different iodine regimens

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Abstract

Background

Thyroid damage occurs during experimental iodine-deficient goiter and involution with iodine supplementation. This study investigated the dynamic microRNAs (miRNAs) expression profiles in iodine-deficient thyroids during adequate and excessive iodine supplementation.

Methods

Twenty-four female Wistar rats were randomly divided into control, low-iodine (LI), LI-1I, and LI-2I groups. The LI-1I and LI-2I groups were fed a LI diet for 12 weeks, followed by a onefold (adequate) or twofold (excessive) physiological dose of iodine for 4 weeks to induce involution. The miRNA expression profiles were evaluated and the potential functions of the differentially expressed miRNAs identified were explored.

Results

In the LI group, 20 miRNAs were downregulated and 8 were upregulated. After involution, 21 miRNAs recovered to the control group levels in the LI-1I group, which was more than the 17 that recovered in the LI-2I group. In addition, 8 new differentially expressed miRNAs were identified in the LI-1I group, which was less than the 13 found in the LI-2I group. Bioinformatics analyses indicated that all differentially expressed miRNAs were involved in different processes and pathways, such as autoimmune thyroid disease and the Ras signaling pathway.

Conclusion

Differentially expressed miRNAs are involved in iodine-deficient goiter formation and involution. Supplementation with adequate, not excessive, iodine may be more beneficial to restore homeostasis.

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References

  1. A. Carle, A. Krejbjerg, P. Laurberg, Epidemiology of nodular goitre. Influence of iodine intake. Best practice & research. Best Pract. Res. Clin. Endocrinol. Metab. 28(4), 465–479 (2014). https://doi.org/10.1016/j.beem.2014.01.001

    Article  CAS  PubMed  Google Scholar 

  2. M. Chaudhary, N. Baisakhiya, G. Singh, Clinicopathological and radiological study of thyroid swelling. Indian J. Otolaryngol. Head Neck Surg. 71(Suppl 1), 893–904 (2019). https://doi.org/10.1007/s12070-019-01616-y

    Article  PubMed  PubMed Central  Google Scholar 

  3. K. Markou, N. Georgopoulos, V. Kyriazopoulou, A.G. Vagenakis, Iodine-induced hypothyroidism. Thyroid 11(5), 501–510 (2001). https://doi.org/10.1089/105072501300176462

    Article  CAS  PubMed  Google Scholar 

  4. A.M. Leung, L.E. Braverman, Iodine-induced thyroid dysfunction. Curr. Opin. Endocrinol. Diabetes Obes. 19(5), 414–419 (2012). https://doi.org/10.1097/MED.0b013e3283565bb2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. W. Teng, Z. Shan, X. Teng, H. Guan, Y. Li, D. Teng, Y. Jin, X. Yu, C. Fan, W. Chong, F. Yang, H. Dai, Y. Yu, J. Li, Y. Chen, D. Zhao, X. Shi, F. Hu, J. Mao, X. Gu, R. Yang, Y. Tong, W. Wang, T. Gao, C. Li, Effect of iodine intake on thyroid diseases in China. N. Engl. J. Med. 354(26), 2783–2793 (2006). https://doi.org/10.1056/NEJMoa054022

    Article  CAS  PubMed  Google Scholar 

  6. P. Laurberg, T. Jorgensen, H. Perrild, L. Ovesen, N. Knudsen, I.B. Pedersen, L.B. Rasmussen, A. Carle, P. Vejbjerg, The Danish investigation on iodine intake and thyroid disease, DanThyr: status and perspectives. Eur. J. Endocrinol. 155(2), 219–228 (2006). https://doi.org/10.1530/eje.1.02210

    Article  CAS  PubMed  Google Scholar 

  7. S. Poncin, A.C. Gérard, M. Boucquey, M. Senou, P.B. Calderon, B. Knoops, B. Lengelé, M.C. Many, I.M. Colin, Oxidative stress in the thyroid gland: from harmlessness to hazard depending on the iodine content. Endocrinology 149(1), 424–433 (2008). https://doi.org/10.1210/en.2007-0951

    Article  CAS  PubMed  Google Scholar 

  8. J.F. Mutaku, J.F. Poma, M.C. Many, J.F. Denef, M.F. van Den Hove, Cell necrosis and apoptosis are differentially regulated during goitre development and iodine-induced involution. J. Endocrinol. 172(2), 375–386 (2002). https://doi.org/10.1677/joe.0.1720375

    Article  CAS  PubMed  Google Scholar 

  9. M.C. Many, J.F. Denef, Iodine and goiter involution. Thyroidology 4(1), 23–26 (1992)

    CAS  PubMed  Google Scholar 

  10. M.C. Many, S. Maniratunga, I. Varis, M. Dardenne, H.A. Drexhage, J.F. Denef, Two-step development of Hashimoto-like thyroiditis in genetically autoimmune prone non-obese diabetic mice: effects of iodine-induced cell necrosis. J. Endocrinol. 147(2), 311–320 (1995). https://doi.org/10.1677/joe.0.1470311

    Article  CAS  PubMed  Google Scholar 

  11. W. Dong, H. Zhang, P. Zhang, X. Li, L. He, Z. Wang, Y. Liu, The changing incidence of thyroid carcinoma in Shenyang, China before and after universal salt iodization. Med. Sci. Monit. 19, 49–53 (2013). https://doi.org/10.12659/msm.883736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. M. Blomberg, U. Feldt-Rasmussen, K.K. Andersen, S.K. Kjaer, Thyroid cancer in Denmark 1943-2008, before and after iodine supplementation. Int. J. Cancer 131(10), 2360–2366 (2012). https://doi.org/10.1002/ijc.27497

    Article  CAS  PubMed  Google Scholar 

  13. G. Wan, R. Mathur, X. Hu, X. Zhang, X. Lu, miRNA response to DNA damage. Trends Biochem. Sci. 36(9), 478–484 (2011). https://doi.org/10.1016/j.tibs.2011.06.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. D.P. Bartel, MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116(2), 281–297 (2004). https://doi.org/10.1016/s0092-8674(04)00045-5

    Article  CAS  PubMed  Google Scholar 

  15. H. Otsu, M. Watanabe, N. Inoue, R. Masutani, Y. Iwatani, Intraindividual variation of microRNA expression levels in plasma and peripheral blood mononuclear cells and the associations of these levels with the pathogenesis of autoimmune thyroid diseases. Clin. Chem. Lab. Med. 55(5), 626–635 (2017). https://doi.org/10.1515/cclm-2016-0449

    Article  CAS  PubMed  Google Scholar 

  16. M. Sun, S. Fang, W. Li, C. Li, L. Wang, F. Wang, Y. Wang, Associations of miR-146a and miR-146b expression and clinical characteristics in papillary thyroid carcinoma. Cancer Biomark. 15(1), 33–40 (2015). https://doi.org/10.3233/cbm-140431

    Article  CAS  PubMed  Google Scholar 

  17. M.E. Graham, R.D. Hart, S. Douglas, F.M. Makki, D. Pinto, A.L. Butler, M. Bullock, M.H. Rigby, J.R. Trites, S.M. Taylor, R. Singh, Serum microRNA profiling to distinguish papillary thyroid cancer from benign thyroid masses. J. Otolaryngol. Head Neck Surg. 44, 33 (2015). https://doi.org/10.1186/s40463-015-0083-5

    Article  PubMed  PubMed Central  Google Scholar 

  18. A. Sondermann, F.M. Andreghetto, A.C. Moulatlet, E. da Silva Victor, M.G. de Castro, F.D. Nunes, L.G. Brandão, P. Severino, MiR-9 and miR-21 as prognostic biomarkers for recurrence in papillary thyroid cancer. Clin. Exp. Metastasis 32(6), 521–530 (2015). https://doi.org/10.1007/s10585-015-9724-3

    Article  CAS  PubMed  Google Scholar 

  19. J. Yu, Z. Shan, W. Chong, J. Mao, Y. Geng, C. Zhang, Q. Xing, W. Wang, N. Li, C. Fan, H. Wang, H. Zhang, W. Teng, Vitamin E ameliorates iodine-induced cytotoxicity in thyroid. J. Endocrinol. 209(3), 299–306 (2011). https://doi.org/10.1530/joe-11-0030

    Article  CAS  PubMed  Google Scholar 

  20. L. Zheng, C. Zhuang, X. Wang, L. Ming, Serum miR-146a, miR-155, and miR-210 as potential markers of Graves’ disease. J. Clin. Lab. Anal. 32(2) (2018). https://doi.org/10.1002/jcla.22266

  21. Q. Qin, X. Wang, N. Yan, R.H. Song, T.T. Cai, W. Zhang, L.J. Guan, F.S. Muhali, J.A. Zhang, Aberrant expression of miRNA and mRNAs in lesioned tissues of Graves’ disease. Cell. Physiol. Biochem. 35(5), 1934–1942 (2015). https://doi.org/10.1159/000374002

    Article  CAS  PubMed  Google Scholar 

  22. Z. Sun, L. Yi, H. Tao, J. Huang, Z. Jin, Y. Xiao, C. Feng, J. Sun, Enhancement of soluble CD28 levels in the serum of Graves’ disease. Cent. Eur. J. Immunol. 39(2), 216–222 (2014). https://doi.org/10.5114/ceji.2014.43726

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. H. Yamada, M. Itoh, I. Hiratsuka, S. Hashimoto, Circulating microRNAs in autoimmune thyroid diseases. Clin. Endocrinol. 81(2), 276–281 (2014). https://doi.org/10.1111/cen.12432

    Article  CAS  Google Scholar 

  24. R.T. Schaller, J.K. Stevenson, Development of carcinoma of the thyroid in iodine-deficient mice. Cancer 19(8), 1063–1080 (1966). 10.1002/1097-0142(196608)19:8<1063::aid-cncr2820190804>3.0.co;2-a

    Article  PubMed  Google Scholar 

  25. S.D. Mitro, L.S. Rozek, P. Vatanasapt, K. Suwanrungruang, I. Chitapanarux, S. Srisukho, H. Sriplung, R. Meza, Iodine deficiency and thyroid cancer trends in three regions of Thailand, 1990-2009. Cancer Epidemiol. 43, 92–99 (2016). https://doi.org/10.1016/j.canep.2016.07.002

    Article  PubMed  Google Scholar 

  26. B. Zha, X. Huang, J. Lin, J. Liu, Y. Hou, G. Wu, Distribution of lymphocyte subpopulations in thyroid glands of human autoimmune thyroid disease. J. Clin. Lab. Anal. 28(3), 249–254 (2014). https://doi.org/10.1002/jcla.21674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. M. Bastemir, R. Emral, G. Erdogan, S. Gullu, High prevalence of thyroid dysfunction and autoimmune thyroiditis in adolescents after elimination of iodine deficiency in the Eastern Black Sea Region of Turkey. Thyroid 16(12), 1265–1271 (2006). https://doi.org/10.1089/thy.2006.16.1265

    Article  CAS  PubMed  Google Scholar 

  28. Y. Luo, A. Kawashima, Y. Ishido, A. Yoshihara, K. Oda, N. Hiroi, T. Ito, N. Ishii, K. Suzuki, Iodine excess as an environmental risk factor for autoimmune thyroid disease. Int. J. Mol. Sci. 15(7), 12895–12912 (2014). https://doi.org/10.3390/ijms150712895

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. G.H. McIntosh, G.B. Jones, D.A. Howard, G.B. Belling, B.J. Potter, B.S. Hetzel, Low-iodine diet for producing iodine deficiency in rats. Aust. J. Biol. Sci. 33(2), 205–211 (1980). https://doi.org/10.1071/bi9800205

    Article  CAS  PubMed  Google Scholar 

  30. W. Chong, W. Chen, W. Teng, Y. Jin, X. Zhang, L. Xi, N. Zhang, N. Man, Y. Tong, Y. Yu, C. Fan, H. Guan, Y. Li, Establish and evaluation ofiodine-deficient animal model. J. Chin. Med. Univ. 34(2), 111–113 (2005). (In Chinese)

    Google Scholar 

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Acknowledgements

We thank Medjaden Bioscience Limited for English editing.

Funding

This work was funded by W.C. (Grant Number 81372970) and J.M. (Grant Number LFWK201702 and LR2019075).

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Authors and Affiliations

Authors

Contributions

Data analysis and writing—original draft preparation: J.Z. and J.M.; methodology: J.Y. and W.C.; project supervision: Z.S. and W.T.; data analysis: J.Z, C.L and J.M.; funding acquisition: W.C. and J.M.; and project administration and writing—review and editing: J.M.

Corresponding author

Correspondence to Jinyuan Mao.

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The authors declare no competing interests.

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All procedures performed in studies involving rats were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Zhao, J., Yu, J., Shan, Z. et al. MicroRNA expression profiles of the thyroid after goiter formation and involution in rats under different iodine regimens. Endocrine 73, 598–608 (2021). https://doi.org/10.1007/s12020-021-02679-0

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