Sibilio, Annarita (2013) Role of Type 3 deiodinase in normal skin and in wound healing processes. [Tesi di dottorato]
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| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Role of Type 3 deiodinase in normal skin and in wound healing processes |
| Autori: | Autore Email Sibilio, Annarita annsib@hotmail.it |
| Data: | 30 Marzo 2013 |
| Numero di pagine: | 48 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | Medicina Molecolare e Biotecnologie Mediche |
| Scuola di dottorato: | Medicina molecolare |
| Dottorato: | Patologia e fisiopatologia molecolare |
| Ciclo di dottorato: | 25 |
| Coordinatore del Corso di dottorato: | nome email Avvedimento, Vittorio Enrico vittorio.avvedimento@unina.it |
| Tutor: | nome email Salvatore, Domenico domsalva@unina.it |
| Data: | 30 Marzo 2013 |
| Numero di pagine: | 48 |
| Parole chiave: | type 3 deiodinase, thyroid hormone, skin, wound healing |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/11 - Biologia molecolare Area 06 - Scienze mediche > MED/04 - Patologia generale Area 06 - Scienze mediche > MED/13 - Endocrinologia |
| Depositato il: | 10 Apr 2013 13:46 |
| Ultima modifica: | 17 Giu 2014 06:04 |
| URI: | http://www.fedoa.unina.it/id/eprint/9279 |
Abstract
The skin is a well-known target of thyroid hormone (TH). TH action is finely controlled by the deiodinase family of enzymes, responsible of the tissue-specific activation and inactivation of the prohormone thyroxine (T4). We report that the type 3 deiodinase (D3), the principal terminator of TH action, is required for the normal epidermal proliferation. D3-depleted keratinocytes show a proliferative defect, associated with a trend toward early differentiation. K14CRE-Dio3Fl/Fl mice, in the absence of D3 only in epidermis, present an alterated epidermal phenotype characterized by a thinner epidermis, reduced levels of K14 (specific marker for the basal proliferating cells) and slowed T4 clearance. These manifestations affect on epidermal regeneration processes in which a proper balance between cellular proliferation and differentiation is strictly required. We found a massive induction of D3 during early phases of wound healing, when the cellular environment requires an increased proliferation necessary to repair the damage. Moreover, K14CRE-Dio3Fl/Fl mice show a defective wound repair compared to WT mice, with a delayed wound closure, caused by a decrease of proliferation. In conclusion, we show that the D3 enzyme is employed to attenuate TH-signaling in skin, providing a striking example of how a circulating hormone can be tissue-specifically attenuated to influence local requirement.
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