Collagen VII half-life at the dermal-epidermal junction zone: implications for mechanisms and therapy of genodermatoses
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 rat...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
29 March 2016
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| In: |
The journal of investigative dermatology
Year: 2016, Jahrgang: 136, Heft: 6, Pages: 1116-1123 |
| ISSN: | 1523-1747 |
| DOI: | 10.1016/j.jid.2016.02.002 |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1016/j.jid.2016.02.002 Verlag, Volltext: http://www.sciencedirect.com/science/article/pii/S0022202X16004838 
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| Verfasserangaben: | Tobias Kühl, Markus Mezger, Ingrid Hausser, Lin T. Guey, Rupert Handgretinger, Leena Bruckner-Tuderman and Alexander Nyström |
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| 520 | |a 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. | ||
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