nvestigation of the role of Rac 1 in a bleomycin - induced scleroderma model using fibroblast - specific Rac 1 knockout mice

1 Division of Oral Biology, University of Western Ontario, London, ON, Canada 2 Centre for Rheumatology, University College London (Royal Free Campus), UK Background Activated adhesive signaling is a hallmark of fibroblasts isolated from 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 bearing a fibroblast-specific deletion of Rac1. Materials and Methods Cutaneous sclerosis was induced by subcutaneous injection of bleomycin. Control groups were treated with phosphate buffered saline (PBS). Mice bearing a fibroblast-specific deletion of Rac1 and control mice were investigated. Dermal thickness, inflammation, collagen production and the number of -smooth muscle actin ( -SMA)-positive cells were determined. The quantity of the collagenspecific amino acid hydroxyproline was also measured. The effects of Rac inhibition were assessed on primary scleroderma fibroblasts. Results Bleomycin treatment induced marked cutaneous thickening, inflammation and fibrosis in control mice. Deletion of Rac1 resulted in resistance to bleomycin-induced fibrosis and inflammation. Rac inhibition alleviated the persistent fibrotic phenotype of scleroderma fibroblasts Conclusion Rac1 expression by fibroblasts is required for fibrogenesis. Inhibition of Rac1 may be a viable method to alleviate the development of cutaneous sclerosis. 2. Th17 and Th1 Subsets are increased in Patients with Systemic Sclerosis