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Original communication| Volume 137, ISSUE 1, P92-101, January 2005

Smooth muscle cell expression of a constitutive active form of human Rac 1 accelerates cutaneous wound repair

  • Hamdy H. Hassanain
    Correspondence
    Reprint requests: Hamdy H. Hassanain, PhD, Heart and Lung Research Institute, Ohio State University, 473 W 12th Avenue, Columbus, OH 43210.
    Affiliations
    From the Department of Surgery and Anesthesiology and the Department of Oral Biology, Ohio State University, Columbus, Ohio; and the Department of Medicine, Duke University Medical Center, Durham, NC
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  • Fawzi Irshaid
    Affiliations
    From the Department of Surgery and Anesthesiology and the Department of Oral Biology, Ohio State University, Columbus, Ohio; and the Department of Medicine, Duke University Medical Center, Durham, NC
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  • Sheik Wisel
    Affiliations
    From the Department of Surgery and Anesthesiology and the Department of Oral Biology, Ohio State University, Columbus, Ohio; and the Department of Medicine, Duke University Medical Center, Durham, NC
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  • John Sheridan
    Affiliations
    From the Department of Surgery and Anesthesiology and the Department of Oral Biology, Ohio State University, Columbus, Ohio; and the Department of Medicine, Duke University Medical Center, Durham, NC
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  • Robert E. Michler
    Affiliations
    From the Department of Surgery and Anesthesiology and the Department of Oral Biology, Ohio State University, Columbus, Ohio; and the Department of Medicine, Duke University Medical Center, Durham, NC
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  • Pascal J. Goldschmidt-Clermont
    Affiliations
    From the Department of Surgery and Anesthesiology and the Department of Oral Biology, Ohio State University, Columbus, Ohio; and the Department of Medicine, Duke University Medical Center, Durham, NC
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      Background

      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.

      Methods

      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 α-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.

      Results

      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.

      Conclusion

      The current studies suggest that Rac 1 activation accelerates the wound healing process and is associated with more efficient angiogenesis at the wound site.
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