Mice Lacking Smad3 Are Protected Against Cutaneous Injury Induced by Ionizing Radiation
| Autor: | Chu-Xia Deng, Catherine D. Sullivan, Makiko Fujii, Christopher Major, Mario A. Anzano, Kathleen C. Flanders, Alidad Arabshahi, Angelo Russo, Anastasia L. Sowers, James B. Mitchell, Anita B. Roberts |
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| Jazyk: | angličtina |
| Rok vydání: | 2002 |
| Předmět: |
Keratinocytes
Pathology medicine.medical_specialty Ratón Cell Survival medicine.medical_treatment Inflammation Pathology and Forensic Medicine Mice Fibrosis Transforming Growth Factor beta medicine Animals Smad3 Protein Receptor Skin Mice Knockout biology integumentary system Growth factor Transforming growth factor beta Fibroblasts medicine.disease Molecular biology DNA-Binding Proteins Radiation Injuries Experimental Cytokine Gamma Rays biology.protein Trans-Activators medicine.symptom Transforming growth factor Regular Articles |
| Popis: | Transforming growth factor-beta (TGF-beta) plays a central role in the pathogenesis of inflammatory and fibrotic diseases, including radiation-induced fibrosis. We previously reported that mice null for Smad3, a key downstream mediator of TGF-beta, show accelerated healing of cutaneous incisional wounds with reduced inflammation and accumulation of matrix. To determine if loss of Smad3 decreases radiation-induced injury, skin of Smad3+/+ [wild-type (WT)] and -/- [knockout (KO)] mice was exposed to a single dose of 30 to 50 Gy of gamma-irradiation. Six weeks later, skin from KO mice showed significantly less epidermal acanthosis and dermal influx of mast cells, macrophages, and neutrophils than skin from WT littermates. Skin from irradiated KO mice exhibited less immunoreactive TGF-beta and fewer myofibroblasts, suggesting that these mice will have a significantly reduced fibrotic response. Although irradiation induced no change in the immunohistochemical expression of the TGF-beta type I receptor, the epidermal expression of the type II receptor was lost after irradiation whereas its dermal expression remained high. Primary keratinocytes and dermal fibroblasts prepared from WT and KO mice showed similar survival when irradiated, as did mice exposed to whole-body irradiation. These results suggest that inhibition of Smad3 might decrease tissue damage and reduce fibrosis after exposure to ionizing irradiation. |
| Databáze: | OpenAIRE |
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