Loss of beta1 integrin in mouse fibroblasts results in resistance to skin scleroderma in a mouse model

Arthritis Rheum. 2009 Sep;60(9):2817-21. doi: 10.1002/art.24801.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism
  • Animals
  • Bleomycin
  • Cell Adhesion / physiology
  • Cells, Cultured
  • Collagen / metabolism
  • Disease Models, Animal
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Gene Deletion
  • Integrin beta1 / genetics*
  • Integrin beta1 / metabolism*
  • Mice
  • Mice, Knockout
  • Scleroderma, Systemic / chemically induced
  • Scleroderma, Systemic / metabolism*
  • Scleroderma, Systemic / prevention & control*
  • Signal Transduction / physiology
  • Skin / metabolism
  • Skin / pathology
  • Skin Diseases / chemically induced
  • Skin Diseases / metabolism*
  • Skin Diseases / prevention & control*

Substances

  • Actins
  • Integrin beta1
  • Bleomycin
  • Collagen