Smooth muscle cell expression of a constitutive active form of human Rac 1 accelerates cutaneous wound repair
| Autor: | Hamdy H. Hassanain, Robert E. Michler, Sheik Wisel, Fawzi I. Irshaid, Pascal J. Goldschmidt-Clermont, John F. Sheridan |
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| Rok vydání: | 2005 |
| Předmět: |
Collagen Type IV
rac1 GTP-Binding Protein Genetically modified mouse Pathology medicine.medical_specialty Enzyme complex Vascular smooth muscle Angiogenesis Gene Expression Neovascularization Physiologic Mice Transgenic Biology Muscle Smooth Vascular Mice Pregnancy medicine Animals Humans Myocyte Transgenes Promoter Regions Genetic Aorta Skin Wound Healing Cell growth Neuropeptides Wild type Hypoxia-Inducible Factor 1 alpha Subunit Actins rac GTP-Binding Proteins Cell biology Mice Inbred CBA Female Surgery Wound healing Transcription Factors |
| Zdroj: | Surgery. 137:92-101 |
| ISSN: | 0039-6060 |
| DOI: | 10.1016/j.surg.2004.06.012 |
| Popis: | Hyperoxia has been shown to improve wound healing; however, the mechanism for such therapeutic effects of oxygen remains hypothetical. Rac 1 regulates a wide variety of cellular activities, including cell proliferation and migration, and also is a key regulator for the activity of the nicotinamide dinucleotide phosphate oxidase the enzyme complex responsible for the production of a large fraction of cellular superoxide.We generated transgenic mice that express either the cDNA of a constitutively active mutant of human Rac 1 (V12 mutant or Rac CA) or the dominant negative isoform (V12 and N17 mutant or Rac DN) in the blood vessels using mouse vascular smooth muscle promoter for alpha-actin. We placed 2 wounds of 6 mm in diameter at the middorsal region of each mouse and allowed about 3 weeks for the wounds to heal.The size of the wounds in Rac CA transgenic mice was reduced relative to wild type mice; healing of Rac DN mice was slower than wild type and Rac CA ( P.05). Blood vessel formation appeared faster in Rac CA mice, a finding associated with enhanced expression of some angiogenic growth factors.The current studies suggest that Rac 1 activation accelerates the wound healing process and is associated with more efficient angiogenesis at the wound site. |
| Databáze: | OpenAIRE |
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