Collagen VII Half-Life at the Dermal-Epidermal Junction Zone: Implications for Mechanisms and Therapy of Genodermatoses.
J Invest Dermatol
; 136(6): 1116-1123, 2016 06.
Article
em En
| MEDLINE
| ID: mdl-26899947
ABSTRACT
The tissue half-life of proteins largely determines treatment frequency of non-gene-editing-based therapies targeting the cause of genodermatoses. Surprisingly, such knowledge is missing for a vast number of proteins involved in pathologies. The dermal-epidermal junction zone is believed to be a rather static structure, but to our knowledge no detailed analysis of the stability of proteins within this zone has been performed. Here, we addressed the in vivo half-life of collagen type VII using genetic ablation of its expression and therapeutic introduction of exogenous collagen VII in a preclinical model. A similar in vivo stability of collagen VII was observed in the skin, tongue, and esophagus, with a half-life of about 1 month. Collagen VII expressed by intradermally injected mesenchymal stromal cells also exhibited a similar half-life. Our study provides key information needed for the development of protein replacement or cell-based therapies for dystrophic epidermolysis bullosa caused by genetic deficiency of collagen VII. Moreover, by showing what we define as an intermediate half-life of collagen VII, our study challenges the view of the dermal-epidermal junction zone as a static structure with very slow turnover.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Terapia Genética
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Epidermólise Bolhosa Distrófica
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Colágeno Tipo VII
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Transplante de Células-Tronco Mesenquimais
Tipo de estudo:
Clinical_trials
Limite:
Animals
/
Humans
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Male
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article