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

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

Research output: Contribution to journalArticle

8 Scopus citations

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 informa-tion 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 clus-tering 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 admin-istration, 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.

Original languageEnglish (US)
Pages (from-to)75-87
Number of pages13
JournalGene Regulation and Systems Biology
Volume2014
Issue number8
DOIs
StatePublished - Oct 24 2013

All Science Journal Classification (ASJC) codes

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Computer Science Applications

Keywords

  • Corticosteroids
  • Gene expression
  • Gene regulation
  • Glucocorticoids
  • Liver
  • Muscle
  • Promoter analysis

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