Triiodothyronine (T3) inhibits hyaluronate synthesis in a human dermal equivalent by downregulation of HAS2
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iiodothyronine (T3) inhibits hyaluronate synthesis in a human dermal equivalent by downregulation of HAS2 Tara Pouyani & Basma H. Sadaka & Suzanne Papp & Lana Schaffer
Received: 19 October 2012 / Accepted: 20 January 2013 / Published online: 9 February 2013 / Editor: T. Okamoto # The Society for In Vitro Biology 2013
Abstract Triiodothyronine (T3) is a thyroid hormone that can have varying effects on skin. In order to assess the effects of T3 on the human dermis, we prepared dermal equivalents using neonatal dermal cells via the process of self-assembly in the presence of differing concentrations of T3. These dermal equivalents were prepared in the absence of serum and a three dimensional matrix allowing for the direct assessment of different concentrations of T3 on dermal extracellular matrix formation. Three different concentrations of T3 were chosen, 20 pM, which is part of the base medium, 0.2 nM T3 and 2 nM T3. We find that selfassembled dermal equivalents formed under these conditions show a progressive “thinning” with increasing T3 concentrations. While we observed no change in total collagen content, inhibition of hyaluronate (HA) synthesis was observed in the 0.2- and 2-nM T3 constructs as compared to the 20-pM construct. Other glycosaminoglycan synthesis was not affected by increasing T3 concentrations. In order to identify the gene(s) responsible for inhibition of HA synthesis in the 2-nM T3 dermal equivalent, we conducted a differential gene array analysis. The results of these experiments demonstrate the differential expression of 40 genes, of these, 34 were upregulated and 6 genes were downregulated. The results from these experiments suggest that downregulation of HAS2 may be responsible for inhibition of hyaluronate synthesis in the self-assembled 2-nM T3 human dermal matrix.
T. Pouyani (*) : B. H. Sadaka Department of Pharmaceutical Sciences, Northeastern University, Bouvé College of Health Sciences, Boston, MA 02115, USA e-mail: [email protected] S. Papp : L. Schaffer DNA Array Core Facility, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA
Keywords Dermal equivalent . Hyaluronic acid . Triiodothyronine . Tissue engineering . Hyaluronate synthase
Introduction Triiodothyronine (T3) is a biologically active thyroid hormone that can have a number of effects on skin and wound healing (Safer et al. 2004; Paus 2010). Both abnormally low and high levels of thyroid hormones can alter the appearance and function of human skin. In hypothyroid humans, the skin is cool and dry, the epidermis is thinner than normal and alopecia may develop (van Beek et al. 2008). Thyrotoxicosis is also associated with certain cutaneous manifestations such as hyperhidrosis. Topical application of T3 can lead to epidermal proliferation and dermal thickening (Safer et al. 2001). The effects of thyroid hormone are mediated principally through T3, which is known to regulate gene expression by binding to the nuclear thyroid hormone receptors known to be expressed in skin (ContrerasJurado et al.
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