Impaired Skin Regeneration and Remodeling after Cutaneous Injury and Chemically Induced Hyperplasia in Taps-Transgenic Mice
| Autor: | Niels Grabe, Peter Angel, Verena Rhiemeier, Maike Hildenbrand, Jochen Hess, Bernd Lahrmann, Bettina Hartenstein |
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| Rok vydání: | 2010 |
| Předmět: |
Keratinocytes
Genetically modified mouse Pathology medicine.medical_specialty Transgene Stratum granulosum Gene Expression Mice Transgenic Human skin Dermatology Filaggrin Proteins Biology Biochemistry Mice medicine Animals Aspartic Acid Endopeptidases Humans Regeneration Promoter Regions Genetic Ubiquitin C Molecular Biology Skin Wound Healing Hyperplasia integumentary system Regeneration (biology) Cell Differentiation Cell Biology medicine.disease Cell biology Mice Inbred C57BL Phenotype medicine.anatomical_structure Lac Operon Carcinogens Tetradecanoylphorbol Acetate Female Cell Division Filaggrin |
| Zdroj: | Journal of Investigative Dermatology. 130:1922-1930 |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2010.54 |
| Popis: | Recently, we identified an AP-1-dependent target gene in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated mouse back skin, which encodes a retroviral-like aspartic proteinase (Taps/Asprv1). Taps expression was detected almost exclusively in stratified epithelia of mouse embryos and adult tissues, and enhanced protein levels were present in several non-neoplastic human skin disorders, implicating a crucial role for differentiation and homeostasis of multilayered epithelia. Here, we generated a mouse model in which Taps transgene expression is under the control of the human ubiquitin C promoter (UBC-Taps). Although no obvious phenotype was observed in normal skin development and homeostasis, these mice showed a significant delay in cutaneous wound closure compared with control animals. Shortly after re-epithelialization, we found an increase in keratinocytes in the stratum granulosum, which express Filaggrin, a late differentiation marker. A hypergranulosum-like phenotype with increased numbers of Filaggrin-positive keratinocytes was also observed in UBC-Taps mice after administration of TPA. In summary, these data show that aberrant Taps expression causes impaired skin regeneration and skin remodeling after cutaneous injury and chemically induced hyperplasia. |
| Databáze: | OpenAIRE |
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