| First Author | Kühl T | Year | 2016 |
| Journal | J Invest Dermatol | Volume | 136 |
| Issue | 6 | Pages | 1116-23 |
| PubMed ID | 26899947 | Mgi Jnum | J:233455 |
| Mgi Id | MGI:5784795 | Doi | 10.1016/j.jid.2016.02.002 |
| Citation | Kuhl T, et al. (2016) Collagen VII Half-Life at the Dermal-Epidermal Junction Zone: Implications for Mechanisms and Therapy of Genodermatoses. J Invest Dermatol 136(6):1116-23 |
| abstractText | 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. |
