OBJECTIVE: Activated adhesive signaling is a hallmark of fibroblasts isolated from the scars of scleroderma (systemic sclerosis) lesions. Beta-1 integrin plays a key role in adhesive signaling. The aim of the present study was to examine the role of beta1 integrin in a mouse model of skin scleroderma using mice bearing a fibroblast-specific deletion of beta1 integrin. METHODS: Cutaneous sclerosis was induced by subcutaneous injection of bleomycin. Control groups were treated with phosphate buffered saline. Mice bearing a fibroblast-specific deletion of beta1 integrin and control mice were investigated. Dermal thickness, 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 and fibrosis in control mice. Conversely, the deletion of beta1 integrin resulted in resistance to bleomycin-induced fibrosis. CONCLUSION: Expression of beta1 integrin by fibroblasts is required for fibrogenesis. Inhibition of beta1 integrin may be a viable method to alleviate the development of cutaneous sclerosis.
OBJECTIVE: Activated adhesive signaling is a hallmark of fibroblasts isolated from the scars of scleroderma (systemic sclerosis) lesions. Beta-1 integrin plays a key role in adhesive signaling. The aim of the present study was to examine the role of beta1 integrin in a mouse model of skin scleroderma using mice bearing a fibroblast-specific deletion of beta1 integrin. METHODS:Cutaneous sclerosis was induced by subcutaneous injection of bleomycin. Control groups were treated with phosphate buffered saline. Mice bearing a fibroblast-specific deletion of beta1 integrin and control mice were investigated. Dermal thickness, 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 and fibrosis in control mice. Conversely, the deletion of beta1 integrin resulted in resistance to bleomycin-induced fibrosis. CONCLUSION: Expression of beta1 integrin by fibroblasts is required for fibrogenesis. Inhibition of beta1 integrin may be a viable method to alleviate the development of cutaneous sclerosis.