Increased expression of microRNA miR-326 in type 1 diabetic patients with ongoing islet autoimmunity

Authors

  • Guido Sebastiani,

    1. Department of Internal Medicine, Endocrine and Metabolic Science and Biochemistry, University of Siena and Umberto Di Mario ONLUS Research Foundation, Siena, Italy
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  • Fabio Arturo Grieco,

    1. Department of Internal Medicine, Endocrine and Metabolic Science and Biochemistry, University of Siena and Umberto Di Mario ONLUS Research Foundation, Siena, Italy
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  • Isabella Spagnuolo,

    1. Department of Internal Medicine, Endocrine and Metabolic Science and Biochemistry, University of Siena and Umberto Di Mario ONLUS Research Foundation, Siena, Italy
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  • Letizia Galleri,

    1. Department of Internal Medicine, Endocrine and Metabolic Science and Biochemistry, University of Siena and Umberto Di Mario ONLUS Research Foundation, Siena, Italy
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  • Dorica Cataldo,

    1. Department of Internal Medicine, Endocrine and Metabolic Science and Biochemistry, University of Siena and Umberto Di Mario ONLUS Research Foundation, Siena, Italy
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  • Francesco Dotta

    Corresponding author
    1. Department of Internal Medicine, Endocrine and Metabolic Science and Biochemistry, University of Siena and Umberto Di Mario ONLUS Research Foundation, Siena, Italy
    • U.O. Diabetologia, University of Siena, Policlinico “Le Scotte”, 3°Lotto-5S, V.le Bracci 18, 53100 Siena, Italy
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Abstract

Background

The current paradigm that microRNAs represent a new layer of gene regulation has generated much interest in this field. MicroRNAs have emerged as important regulatory factors involved in the developmental processes and in the regulation of insulin secretion and signalling. Furthermore, recent studies revealed an altered microRNA profiling in lymphocytes of patients with autoimmune diseases like multiple sclerosis, in which a hyperexpression of miR-326 was reported. Here, we analysed the expression levels of miR-326 in peripheral blood lymphocytes from type 1 diabetic (T1D) patients in relationship with ongoing islet autoimmunity.

Methods

Peripheral blood lymphocytes were obtained from 19 T1D patients; 4/19 patients were positive for both glutamic acid decarboxylase (GAD) and islet cell antigen 512 autoantibodies; 10/19 were single GAD or IA-2 Ab positive and 5/19 were GAD antibodies and IA-2 antibodies (IA-2A) negative. Quantitative analysis of miR-326 was performed using specific stem–loop primers followed by real-time polymerase chain reaction. All values were normalized to endogenous control U6.

Results

miR-326 resulted increased in Ab-positive versus Ab-negative T1D subjects. Its expression levels were 2.05 ± 0.38-fold increased in peripheral blood lymphocytes from patients expressing both GADA and IA-2A and 2.93 ± 0.46-fold increased in single Ab-positive versus Ab-negative individuals (p < 0.05).

Conclusion

In conclusion, we have shown that miR-326 is expressed at higher levels in T1D subjects with ongoing islet autoimmunity, similar to what has been observed in multiple sclerosis, in which levels of this microRNA were highly correlated with disease severity. Interestingly, an online search of miR-326 predicted targets revealed vitamin D receptor and Erythroblastosis virus E26 oncogene homologue 1, two molecules highly involved in immune regulation. Copyright © 2011 John Wiley & Sons, Ltd.

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