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Horm Metab Res 2016; 48(08): 550-557
DOI: 10.1055/s-0042-106898
Endocrine Research
© Georg Thieme Verlag KG Stuttgart · New York

Differential Expression of Glucocorticoid Receptor Noncoding RNA Repressor Gas5 in Autoimmune and Inflammatory Diseases

T. Mayama
1   Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, USA
2   Present address: Department of Integrate Bioscience, Graduate School of Medical and Pharmaceutical Sciences, Chiba University, Chiba, Japan
,
A. K. Marr
3   Division of Genetics, Sidra Medical and Research Center, Doha, Qatar
,
T. Kino
1   Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, USA
3   Division of Genetics, Sidra Medical and Research Center, Doha, Qatar
› Author Affiliations
Further Information

Publication History

received 03 February 2016

accepted 12 April 2016

Publication Date:
23 May 2016 (online)

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Abstract

Glucocorticoids have strong regulatory actions on the immune system and act as potent therapeutic compounds for autoimmune and inflammatory diseases. We previously reported that the long noncoding RNA growth arrest-specific 5 (Gas5), which accumulates inside the cells in response to cellular starvation/growth arrest, functions as a potent repressor of the glucocorticoid receptor (GR) through its RNA “glucocorticoid response element (GRE)”. To evaluate potential roles of Gas5 in immune-related disorders, we examined Gas5 RNA levels in various autoimmune, inflammatory, and infectious diseases using the microarray data available in the Gene Expression Omnibus. We found that Gas5 levels were altered in whole blood or leukocytes of the patients with rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis, and sarcoidosis. Gas5 levels were also altered in infectious diseases, such as by the human immunodeficiency virus type-1 and influenza virus, and bacterial sepsis. In our experimental analysis using mice, Gas5 levels were kept at high basal levels and did not respond to fasting in immune organs, such as spleen and thymus, while its levels in metabolic organs, including liver, fat, and skeletal muscles, were low at baseline and were highly elevated upon this treatment, possibly through suppression of the mTOR pathway. These results suggest that Gas5 plays a role in the regulation of immune functions and pathogenesis/pathophysiology of autoimmune, inflammatory, and infectious diseases in part through modulation of the GR transcriptional activity via its decoy RNA “GRE”. Changes in the Gas5 levels may also influence disease response to immunosuppressive glucocorticoid therapy.

Key words

autoimmune diseases - fasting - glucocorticoids - mammalian target of rapamycin (mTOR) - tissue glucocorticoid sensitivity
 

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