Nexus between epidermolysis bullosa and transcriptional regulation by thyroid hormone in epidermal keratinocytes.
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.
Tomic-Canic
Marjana
M
The Departments of Dermatology and Biochemistry, and the NYU Cancer Institute, New York University School of Medicine, 550 First Avenue, New York, New York, USA.
Stojadinovic
Olivera
O
Lee
Brian
B
Walsh
Rebecca
R
Blumenberg
Miroslav
M
D002454:Cell Differentiation; D004817:Epidermis / Q000378:metabolism*; D004820:Epidermolysis Bullosa / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015603:Keratinocytes / Q000166:cytology*; D008954:Models, Biological; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D018075:RNA, Complementary / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013963:Thyroid Hormones / Q000378:metabolism*; D014158:Transcription, Genetic
D018075:RNA, Complementary; D018160:Receptors, Cytoplasmic and Nuclear; D013963:Thyroid Hormones