Healing of burn wounds in transgenic mice overexpressing transforming growth factor-beta 1 in the epidermis
| Autor: | Aziz Ghahary, Teddy Chan, Liju Yang, Jack Demare, Paul G. Scott, Takashi Iwashina, Edward E. Tredget |
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| Rok vydání: | 2001 |
| Předmět: |
Genetically modified mouse
Keratinocytes Keratin 14 medicine.medical_treatment Transgene Recombinant Fusion Proteins Mice Transgenic Biology Collagen Type I Pathology and Forensic Medicine Transforming Growth Factor beta1 Mice Transforming Growth Factor beta medicine Animals Humans RNA Messenger Transgenes Promoter Regions Genetic Skin Wound Healing Epidermis (botany) integumentary system Growth factor Lasers Keratin-14 Regular Article Transforming growth factor beta Immunohistochemistry Hydroxyproline Gene Expression Regulation Immunology Cancer research biology.protein Keratins Epidermis Wound healing Burns Cell Division Transforming growth factor |
| Zdroj: | The American journal of pathology. 159(6) |
| ISSN: | 0002-9440 |
| Popis: | Transforming growth factor-beta (TGF-beta) isoforms are multifunctional cytokines that play an important role in wound healing. Transgenic mice overexpressing TGF-beta in the skin under control of epidermal-specific promoters have provided models to study the effects of increased TGF-beta on epidermal cell growth and cutaneous wound repair. To date, most of these studies used transgenic mice that overexpress active TGF-beta in the skin by modulating the latency-associated-peptide to prevent its association with active TGF-beta. The present study is the first to use transgenic mice that overexpress the natural form of latent TGF-beta 1 in the epidermis, driven by the keratin 14 gene promoter to investigate the effects of locally elevated TGF-beta 1 on the healing of partial-thickness burn wounds made on the back of the mice using a CO(2) laser. Using this model, we demonstrated activation of latent TGF-beta after wounding and determined the phenotypes of burn wound healing. We found that introduction of the latent TGF-beta1 gene into keratinocytes markedly increases the release and activation of TGF-beta after burn injury. Elevated local TGF-beta significantly inhibited wound re-epithelialization in heterozygous (42% closed versus 92% in controls, P0.05) and homozygous (25% versus 92%, P0.01) animals at day 12 after wounding. Interestingly, expression of type I collagen mRNA and hydroxyproline significantly increased in the wounds of transgenic mice, probably as a result of a paracrine effect of the transgene. |
| Databáze: | OpenAIRE |
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