Role of Rac1 in a bleomycin-induced scleroderma model using fibroblast-specific Rac1-knockout mice
- PMID: 18576327
- DOI: 10.1002/art.23595
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.
Conclusion: Rac1 expression by fibroblasts is required for fibrogenesis. Inhibition of Rac1 may be a viable method to alleviate the development of cutaneous sclerosis.
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