Collagen VII half-life at the dermal-epidermal junction zone

• Verfasst von: Kühl, Tobias Hans-Jürgen [VerfasserIn]
• Verfasst von: Haußer-Siller, Ingrid [VerfasserIn]
• Titel: Collagen VII half-life at the dermal-epidermal junction zone
• Titelzusatz: implications for mechanisms and therapy of genodermatoses
• Verf.angabe: Tobias Kühl, Markus Mezger, Ingrid Hausser, Lin T. Guey, Rupert Handgretinger, Leena Bruckner-Tuderman and Alexander Nyström
• E-Jahr: 2016
• Jahr: 29 March 2016
• Umfang: 8 S.
• Fussnoten: Gesehen am 04.09.2019
• Titel Quelle: Enthalten in: The journal of investigative dermatology
• Ort Quelle: Amsterdam : Elsevier, 1938
• Jahr Quelle: 2016
• Band/Heft Quelle: 136(2016), 6, Seite 1116-1123
• ISSN Quelle: 1523-1747
• DOI: doi:10.1016/j.jid.2016.02.002
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1675904855

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.