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Nguyen TT, Almon RR, Dubois DC, et al. Tissue-specific gene expression and regulation in liver and muscle following chronic corticosteroid administration. Gene Regul Syst Bio. 2014;8:75-87doi: 10.4137/GRSB.S13134.
Nguyen, T. T., Almon, R. R., Dubois, D. C., Sukumaran, S., Jusko, W. J., & Androulakis, I. P. (2014). Tissue-specific gene expression and regulation in liver and muscle following chronic corticosteroid administration. Gene regulation and systems biology, 875-87. https://doi.org/10.4137/GRSB.S13134
Nguyen, Tung T, et al. "Tissue-specific gene expression and regulation in liver and muscle following chronic corticosteroid administration." Gene regulation and systems biology vol. 8 (2014): 75-87. doi: https://doi.org/10.4137/GRSB.S13134
Nguyen TT, Almon RR, Dubois DC, Sukumaran S, Jusko WJ, Androulakis IP. Tissue-specific gene expression and regulation in liver and muscle following chronic corticosteroid administration. Gene Regul Syst Bio. 2014 Mar 10;8:75-87. doi: 10.4137/GRSB.S13134. eCollection 2014. PMID: 24653645; PMCID: PMC3956809.
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Gene Regul Syst Bio. 2014 Mar 10;8:75-87. doi: 10.4137/GRSB.S13134. eCollection 2014.

Tissue-specific gene expression and regulation in liver and muscle following chronic corticosteroid administration.

Gene regulation and systems biology

Tung T Nguyen, Richard R Almon, Debra C Dubois, Siddharth Sukumaran, William J Jusko, Ioannis P Androulakis

Affiliations

  1. BioMaPS Institute for Quantitative Biology, Rutgers University, Piscataway, NJ, USA.
  2. Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY, USA. ; Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA. ; New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA.
  3. Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY, USA. ; Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
  4. Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA.
  5. Department of Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, USA. ; New York State Center of Excellence in Bioinformatics and Life Sciences, Buffalo, NY, USA.
  6. Biomedical Engineering Department, Rutgers University, Piscataway, NJ, USA. ; Chemical and Biochemical Engineering Department, Rutgers University, Piscataway, NJ, USA.

PMID: 24653645 PMCID: PMC3956809 DOI: 10.4137/GRSB.S13134

Abstract

Although corticosteroids (CSs) affect gene expression in multiple tissues, the array of genes that are regulated by these catabolic steroids is diverse, highly tissue specific, and depends on their functions in the tissue. Liver has many important functions in performing and regulating diverse metabolic processes. Muscle, in addition to its mechanical role, is critical in maintaining systemic energy homeostasis and accounts for about 80% of insulin-directed glucose disposal. Consequently, a better understanding of CS pharmacogenomic effects in these tissues would provide valuable information regarding the tissue-specificity of transcriptional dynamics, and would provide insights into the underlying molecular mechanisms of action for both beneficial and detrimental effects. We performed an integrated analysis of transcriptional data from liver and muscle in response to methylprednisolone (MPL) infusion, which included clustering and functional annotation of clustered gene groups, promoter extraction and putative transcription factor (TF) identification, and finally, regulatory closeness (RC) identification. This analysis allowed the identification of critical transcriptional responses and CS-responsive functions in liver and muscle during chronic MPL administration, the prediction of putative transcriptional regulators relevant to transcriptional responses of CS-affected genes which are also potential secondary bio-signals altering expression levels of target-genes, and the exploration of the tissue-specificity and biological significance of gene expression patterns, CS-responsive functions, and transcriptional regulation. The analysis provided an integrated description of the genomic and functional effects of chronic MPL infusion in liver and muscle.

Keywords: corticosteroids; gene expression; gene regulation; glucocorticoids; liver; muscle; promoter analysis

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