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Annals of Hematology

, Volume 92, Issue 7, pp 953–960 | Cite as

Low expression of glucocorticoid receptor alpha isoform in adult immune thrombocytopenia correlates with glucocorticoid resistance

  • Liangliang Ma
  • Meiyun FangEmail author
  • Yan Liang
  • Yang Xiang
  • Zhilin Jia
  • Xiuli Sun
  • Yi Wang
  • Jixia Qin
Original Article

Abstract

The expression of glucocorticoid receptor (GR) isoforms has been linked to glucocorticoid (GC) resistance in various diseases treated with GC. However, existing data are conflicting in these diseases, and little information is available regarding immune thrombocytopenia (ITP). To further investigate the role of GR isoforms in GC resistance in adult ITP patients, we measured the mRNA expression of GR isoforms (GRα, GRβ, GRγ, GRp) in peripheral blood mononuclear cells (PBMC) from 54 newly diagnosed ITP patients, including GC-sensitive (GCS) and GC-resistant (GCR) patients and 35 healthy volunteers. The GRα and GRβ proteins in PBMC, nuclear factor-κB (NF-κB), and activator protein-1 (AP-1) in the nucleus were detected by Western blotting. Compared to normal subjects, both GRα and GRβ mRNAs were significantly increased in ITP patients (p < 0.05), while there was no significant difference in the mRNA expression of GRγ and GRp. Compared to GCR patients, the expressions of GRα mRNA and GRα protein were significantly higher in GCS patients (p < 0.05). Moreover, no significant difference in the mRNA expression of the GRβ, GRγ, and GRp isoforms was observed between GCS and GCR patients and the GRβ protein could not be detected. Compared to GCS group, the expression of p65/NF-κB was significantly higher in the GCR group (p < 0.05). Overall, we did not find differences in c-Jun/AP-1 protein expression between GCS and GCR patients. In summary, GC resistance in adult ITP patients is associated with a reduced expression of GRα, which may be related with increased NF-κB. GRβ was very low and may not be involved in GC resistance in adult ITP, warranting further exploration.

Keywords

Glucocorticoid receptor Glucocorticoid resistance Immune thrombocytopenia Nuclear factor -κB Activator protein-1 

Notes

Acknowledgments

The authors would like to thank Prof. Jing Liu and Doctor Peng Liu (the Regenerative Medicine Experiment Center, the First Affiliated Hospital, Dalian Medical University, China) for their technical guidance. We thank all the anonymous reviewers for their helpful suggestions on the quality improvement of our paper. This work was partially supported by a grant from the Key Clinical Research Project of Public Health Ministry of China, Commonwealth Trade for Scientific Research (200802031), Clinical Research Project of Chinese Medical Doctor Association (20100136), and Scientific Research Project of Dalian City Committee of Science and Technology (2009E12SF166).

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Liangliang Ma
    • 1
  • Meiyun Fang
    • 1
    Email author
  • Yan Liang
    • 1
  • Yang Xiang
    • 2
  • Zhilin Jia
    • 1
  • Xiuli Sun
    • 1
  • Yi Wang
    • 1
  • Jixia Qin
    • 1
  1. 1.Department of Hematology, the First Affiliated HospitalDalian Medical UniversityDalianPeople’s Republic of China
  2. 2.Department of Hematology210 Hospital of Chinese People’s Liberation ArmyDalianChina

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