title: Hydrocortisone and triiodothyronine regulate hyaluronate synthesis in a tissue-engineered human dermal equivalent through independent pathways.
abstract: Hydrocortisone (HC) and triiodothyronine (T3) have both been shown to be capable of independently inhibiting hyaluronate (HA, hyaluronic acid) synthesis in a self-assembled human dermal equivalent (human dermal matrix). We sought to investigate the action of these two hormones in concert on extracellular matrix formation and HA inhibition in the tissue engineered human dermal matrix. To this end, neonatal human dermal fibroblasts were cultured in defined serum-free medium for 21 days in the presence of each hormone alone, or in combination, in varying concentrations. Through a process of self-assembly, a substantial dermal extracellular matrix formed that was characterized. The results of these studies demonstrate that combinations of the hormones T3 and hydrocortisone showed significantly higher levels of hyaluronate inhibition as compared to each hormone alone in the human dermal matrix. In order to gain preliminary insight into the genes regulating HA synthesis in this system, a differential gene array analysis was conducted in which the construct prepared in the presence of 200 μg/mL HC and 0.2 nM T3 was compared to the normal construct (0.4 μg/mL HC and 20 pM T3). Using a GLYCOv4 gene chip containing approximately 1260 human genes, we observed differential expression of 131 genes. These data suggest that when these two hormones are used in concert a different mechanism of inhibition prevails and a combination of degradation and inhibition of HA synthesis may be responsible for HA regulation in the human dermal matrix.
authors.affiliation: Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115, USA.
authors.forename: Madhura
authors.initials: M
authors.lastname: Deshpande
authors.affiliation: DNA Array Core Facility, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Papp
authors.affiliation: DNA Array Core Facility, The Scripps Research Institute, 10550 N Torrey Pines Rd, La Jolla, CA 92037, USA.
authors.forename: Lana
authors.initials: L
authors.lastname: Schaffer
authors.affiliation: Department of Pharmaceutical Sciences, Bouvé College of Health Sciences, Northeastern University, Boston, MA 02115, USA. Electronic address: tarapouyani@gmail.com.
authors.forename: Tara
authors.initials: T
authors.lastname: Pouyani
mesh_terms: D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology; D020869:Gene Expression Profiling; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000096:biosynthesis*; D006854:Hydrocortisone / Q000494:pharmacology*; D007231:Infant, Newborn; D020411:Oligonucleotide Array Sequence Analysis; D017768:Skin, Artificial; D023822:Tissue Engineering; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D006025:Glycosaminoglycans; D014284:Triiodothyronine; D006820:Hyaluronic Acid; D006854:Hydrocortisone
keywords: Dermal equivalent; Gene array profiling; Hyaluronic acid; Hydrocortisone; Tissue engineering; Triiodothyronine