Loss of beta1 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 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.


CONCLUSIONS
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.
Liu
Shangxi
S
University of Western Ontario, London, Ontario, Canada.
Kapoor
Mohit
M
Denton
Christopher P
CP
Abraham
David J
DJ
Leask
Andrew
A
D000199:Actins / Q000378:metabolism; D000818:Animals; D001761:Bleomycin; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D017353:Gene Deletion; D019012:Integrin beta1 / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D012595:Scleroderma, Systemic / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control*
D000199:Actins; D019012:Integrin beta1; D001761:Bleomycin; D003094:Collagen