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


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.


CONCLUSIONS
The current studies suggest that Rac 1 activation accelerates the wound healing process and is associated with more efficient angiogenesis at the wound site.
Hassanain
Hamdy H
HH
Department of Surgery and Anesthesiology, Ohio State University, 473 W. 12th Avenue, Columbus, OH 43210, USA.
Irshaid
Fawzi
F
Wisel
Sheik
S
Sheridan
John
J
Michler
Robert E
RE
Goldschmidt-Clermont
Pascal J
PJ
D000199:Actins / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000502:physiology; D024141:Collagen Type IV / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism*; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D012867:Skin / Q000098:blood supply* / Q000293:injuries; D014157:Transcription Factors / Q000378:metabolism; D019076:Transgenes / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein
D000199:Actins; D024141:Collagen Type IV; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009479:Neuropeptides; C107953:RAC1 protein, human; D014157:Transcription Factors; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein