title: Role of Rac1 in a bleomycin-induced scleroderma model using fibroblast-specific Rac1-knockout mice.
abstract: OBJECTIVE
  Activated adhesive signaling is a hallmark of fibroblasts isolated from the scars of scleroderma (systemic sclerosis [SSc]) lesions. Rac1 plays a key role in adhesive signaling. The aim of the present study was to examine the role of Rac1 in bleomycin-induced scleroderma, using mice with a fibroblast-specific deletion of Rac1.
  
  
  METHODS
  Cutaneous sclerosis was induced by subcutaneous injection of bleomycin. Control groups were treated with phosphate buffered saline. Mice with a fibroblast-specific deletion of Rac1 and control mice were investigated. Dermal thickness, inflammation, collagen production, and the number of alpha-smooth muscle actin-positive cells were determined. The quantity of the collagen-specific amino acid hydroxyproline was also measured.
  
  
  RESULTS
  Bleomycin treatment induced marked cutaneous thickening, inflammation, and fibrosis in control mice. Conversely, deletion of Rac1 resulted in resistance to bleomycin-induced fibrosis and inflammation.
  
  
  CONCLUSIONS
  Rac1 expression by fibroblasts is required for fibrogenesis. Inhibition of Rac1 may be a viable method to alleviate the development of cutaneous sclerosis.
authors.affiliation: University of Western Ontario, London, Ontario, Canada.
authors.forename: Shangxi
authors.initials: S
authors.lastname: Liu
authors.forename: Mohit
authors.initials: M
authors.lastname: Kapoor
authors.forename: Xu
authors.initials: X
authors.lastname: Shi-wen
authors.forename: Laura
authors.initials: L
authors.lastname: Kennedy
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Denton
authors.forename: Michael
authors.initials: M
authors.lastname: Glogauer
authors.forename: David J
authors.initials: DJ
authors.lastname: Abraham
authors.forename: Andrew
authors.initials: A
authors.lastname: Leask
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects; D001761:Bleomycin / Q000009:adverse effects; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism*; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000235:genetics*; D012594:Scleroderma, Localized / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D020744:rac GTP-Binding Proteins / Q000235:genetics*; D020830:rac1 GTP-Binding Protein
chemical_list: D000903:Antibiotics, Antineoplastic; D009479:Neuropeptides; C484602:Rac1 protein, mouse; D001761:Bleomycin; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein