Sibilio, Annarita (2013) Role of Type 3 deiodinase in normal skin and in wound healing processes. [Tesi di dottorato]


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Item Type: Tesi di dottorato
Resource language: English
Title: Role of Type 3 deiodinase in normal skin and in wound healing processes
Date: 30 March 2013
Number of Pages: 48
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Molecolare e Biotecnologie Mediche
Scuola di dottorato: Medicina molecolare
Dottorato: Patologia e fisiopatologia molecolare
Ciclo di dottorato: 25
Coordinatore del Corso di dottorato:
Avvedimento, Vittorio
Date: 30 March 2013
Number of Pages: 48
Keywords: 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
Date Deposited: 10 Apr 2013 13:46
Last Modified: 17 Jun 2014 06:04

Collection description

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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