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Arthritis Rheum. 2008 Jul;58(7):2189-95. doi: 10.1002/art.23595.

Role of Rac1 in a bleomycin-induced scleroderma model using fibroblast-specific Rac1-knockout mice.

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1
University of Western Ontario, London, Ontario, Canada.

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.

CONCLUSION:

Rac1 expression by fibroblasts is required for fibrogenesis. Inhibition of Rac1 may be a viable method to alleviate the development of cutaneous sclerosis.

PMID:
18576327
DOI:
10.1002/art.23595
[Indexed for MEDLINE]
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