title: Triiodothyronine (T3) inhibits hyaluronate synthesis in a human dermal equivalent by downregulation of HAS2.
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 self-assembled 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.
authors: Department of Pharmaceutical Sciences, Northeastern University, Bouvé College of Health Sciences, Boston, MA, 02115, USA. tarapouyani@gmail.com
authors: Tara
authors: T
authors: Pouyani
authors: Basma H
authors: BH
authors: Sadaka
authors: Suzanne
authors: S
authors: Papp
authors: Lana
authors: L
authors: Schaffer
mesh_terms: D002460:Cell Line; D003094:Collagen / Q000378:metabolism; D020405:Dermis / Q000254:growth & development* / Q000378:metabolism; D015536:Down-Regulation; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D006820:Hyaluronic Acid / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D006821:Hyaluronoglucosaminidase / Q000378:metabolism*; D023822:Tissue Engineering; D014284:Triiodothyronine / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D014284:Triiodothyronine; D006820:Hyaluronic Acid; D003094:Collagen; D006821:Hyaluronoglucosaminidase
references: J Clin Endocrinol Metab. 1987 Feb;64(2):334-9
references: 3793852
references: Nucleic Acids Res. 2003 Feb 15;31(4):e15
references: 12582260
references: J Clin Invest. 1982 Nov;70(5):1066-73
references: 6813355
references: J Clin Endocrinol Metab. 2005 Feb;90(2):936-43
references: 15507505
references: Glycobiology. 2000 Mar;10(3):283-93
references: 10704527
references: Plast Reconstr Surg. 1973 Jan;51(1):71-5
references: 4265750
references: J Clin Endocrinol Metab. 2008 Nov;93(11):4381-8
references: 18728176
references: In Vitro Cell Dev Biol Anim. 2009 Sep;45(8):430-41
references: 19533257
references: Endocrinology. 2004 May;145(5):2357-61
references: 14736740
references: J Invest Dermatol. 2010 Jan;130(1):7-10
references: 20010860
references: Bioinformatics. 2003 Jan 22;19(2):185-93
references: 12538238
references: J Biol Chem. 2011 Jul 8;286(27):24079-88
references: 21566120
references: Endocr Rev. 1989 Aug;10(3):366-91
references: 2673756
references: Thyroid. 2001 Aug;11(8):717-24
references: 11525263
references: J Cutan Pathol. 1974;1(3):113-6
references: 4620275
references: Matrix. 1990 Oct;10(5):306-13
references: 2150688
references: Matrix Biol. 2002 Jan;21(1):25-9
references: 11827789
references: Glycobiology. 2003 Dec;13(12):105R-115R
references: 14514708
references: IUBMB Life. 2002 Oct;54(4):195-9
references: 12512858
references: Endocrinology. 2005 Oct;146(10):4425-30
references: 15976059
references: J Lab Clin Med. 1967 Jun;69(6):950-9
references: 4164902
references: In Vitro Cell Dev Biol Anim. 2012 Sep;48(8):493-506
references: 22956043
references: FEBS Lett. 1984 Aug 20;174(1):34-7
references: 6468657
references: Glycobiology. 2000 Mar;10(3):273-81
references: 10704526
references: Stat Appl Genet Mol Biol. 2004;3:Article3
references: 16646809
references: Biotechniques. 2001 Jan;30(1):38-40, 42
references: 11196318
references: Pathol Biol (Paris). 2005 Sep;53(7):372-82
references: 16085113