Nexus Between Epidermolysis Bullosa and Transcriptional Regulation by Thyroid Hormone in Epidermal Keratinocytes
Year: 2008
Type: article
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 beta4, 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.
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: bronze
Funders: Dystrophic Epidermolysis Bullosa Research Association of America, National Institutes of Health, National Institute of Nursing Research, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Center for Research Resources
Awards: PHYSIOLOGY AND MOLECULAR DETERMINANTS OF DIABETES, Epidermal Genes and Their Regulators in Wound Healing, EFFECTS OF IKKB and NFkB IN INSULIN RESISTANCE, IKK MEDIATED INSULIN RESISTANCE AND IN VIVO REVERSAL, General Clinical Research Center, General Clinical Research Center, Micro-RNA Molecules as Regulators of Diabetic Wound Healing, GLUCOCORTICOIDS IN EPIDERMIS: MECHANISMS OF ACTION, Diabetes Research Center
OpenAlex ID: W1982718618
