Loss of β1 Integrin in Mouse Fibroblasts Results in Resistance to Skin Scleroderma in a Mouse Model

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 beta 1 integrin in a mouse model of skin scleroderma using mice bearing a fibroblast-specific deletion of beta 1 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 beta 1 integrin and control mice were investigated. Dermal thickness, collagen production, and the number of a-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 beta 1 integrin resulted in resistance to bleomycin-induced fibrosis. Conclusion. Expression of beta 1 integrin by fibroblasts is required for fibrogenesis. Inhibition of beta 1 integrin may be a viable method to alleviate the development of cutaneous sclerosis.