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Loss of beta 1 Integrin in Mouse Fibroblasts Results in Resistance to Skin Scleroderma in a Mouse Model

Liu, SX; Kapoor, M; Denton, CP; Abraham, DJ; Leask, A; (2009) Loss of beta 1 Integrin in Mouse Fibroblasts Results in Resistance to Skin Scleroderma in a Mouse Model. ARTHRITIS RHEUM , 60 (9) 2817 - 2821. 10.1002/art.24801.

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Abstract

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.

Type: Article
Title: Loss of beta 1 Integrin in Mouse Fibroblasts Results in Resistance to Skin Scleroderma in a Mouse Model
DOI: 10.1002/art.24801
Keywords: MATRIX, CONTRACTION, FIBROSIS
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
URI: http://discovery.ucl.ac.uk/id/eprint/97863
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