Abstract
Aims
Early studies have identified type 1 diabetes mellitus (T1DM) as a disease that is caused by the autoimmune destruction of the insulin-producing pancreatic β-cells. Genetics, environment and the immune pathogenesis of T1DM are three major pillars of T1DM research. We try to understand the changes in the gene expression profile during the pathogenesis of T1DM.
Methods
We performed a systematic search in the Gene Expression Omnibus (GEO) database for microarray studies of T1DM with samples taken at or before the T1DM onset.
Results
The results of an integrated analysis of different GEO datasets and a comparison of the gene expression level in T1DM samples taken at the time of appearance of the islet autoantibodies, 1 year before T1DM onset, and at the time of T1DM onset showed that CD274, which encodes PD-L1, was up-regulated in the newly onset T1DM samples. CD274 had a stable expression level in the control samples but showed a gradual up-regulation from the appearance of autoantibodies to the onset of T1DM.
Conclusions
These results indicate that CD274 up-regulation in T1DM is correlated with disease pathogenesis. PD-L1 might play a protective role in preventing the pancreatic islets from autoimmune destruction, which may help researchers find strategies for preventing the destruction process of pancreas β-cells in T1DM.
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Acknowledgements
This study was supported by grants from the National Natural Science Foundation of China (81471041, to Ji Hu), the National Natural Science Foundation of China (8160030570, to Chen Fang) and the National Natural Science Foundation of China (81502865, to Yun Huang).
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C. F wrote the manuscript, Y. F. P and Y. H. searched the library and reviewed all of the articles. H. H. Z. and X. H. C. extracted the data, H. M. G. and S. C. L. prepared the tables and X. Y. J. and J. H. prepared figures. All authors reviewed the manuscript.
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All procedures performed in studies involving human participants 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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This article does not contain any studies with human or animal subjects performed by the any of the authors.
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Informed consent was obtained from all patients for being included in the study.
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Managed by Massimo Federici.
Chen Fang and Yun Huang are co-first authors.
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Fang, C., Huang, Y., Pei, Y. et al. Genome-wide gene expression profiling reveals that CD274 is up-regulated new-onset type 1 diabetes mellitus. Acta Diabetol 54, 757–767 (2017). https://doi.org/10.1007/s00592-017-1005-y
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DOI: https://doi.org/10.1007/s00592-017-1005-y