Loss of β1 integrin in mouse fibroblasts results in resistance to skin scleroderma in a mouse model

✍ Scribed by Shangxi Liu; Mohit Kapoor; Christopher P. Denton; David J. Abraham; Andrew Leask

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 279 KB
• Volume: 60
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.24801

✦ Synopsis

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 β1 integrin in a mouse model of skin scleroderma using mice bearing a fibroblast‐specific deletion of β1 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 β1 integrin and control mice were investigated. Dermal thickness, collagen production, and the number of α‐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 β1 integrin resulted in resistance to bleomycin‐induced fibrosis.

Conclusion

Expression of β1 integrin by fibroblasts is required for fibrogenesis. Inhibition of β1 integrin may be a viable method to alleviate the development of cutaneous sclerosis.