Nexus between epidermolysis bullosa and transcriptional regulation by thyroid hormone in epidermal keratinocytes

Marjana Tomic-Canic, Olivera Stojadinovic, Brian Lee, Rebecca Walsh, Miroslav Blumenberg

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Thyroid hormone, T3, through the interaction of its receptor with the recognition sequences in the DNA, regulates gene expression. This regulation includes the promoter activity of keratin genes. The receptor shares coregulators with other members of the nuclear receptor family, including RXR. Intending to define the transcriptional effects of thyroid hormones in keratinocytes, we used Affymetrix microarrays to comprehensively compare the genes expressed in T3-treated and untreated human epidermal keratinocytes. The transcriptomes were compared at 1, 4, 24, 48, and 72 hours. Surprisingly, T3 induced only 9 and suppressed 28 genes, much fewer than expected. Significantly, genes associated with epidermolysis bullosa, a set of inherited blistering skin diseases, were found statistically highly overrepresented among the suppressed genes. These genes include Integrin β4, Plectin, Collagen XVII, MMP1, MMP3, and MMP14. The data imply that in keratinocytes T3 could suppresses the remodeling by, attachment to, and production of extracellular matrix. The results suggest that topical treatment with T3 may be effective for alleviation of symptoms in patients with epidermolysis bullosa.

Original languageEnglish
Pages (from-to)45-49
Number of pages5
JournalClinical and Translational Science
Volume1
Issue number1
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

    Fingerprint

Keywords

  • Blistering
  • Differentiation
  • Extracellular matrix
  • Microarrays
  • Nuclear receptors
  • Transcriptional profiling

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this