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Increased expression levels of integrin alphavbeta5 on scleroderma fibroblasts
Yoshihide Asano1, Hironobu Ihn, Kenichi Yamane
1Department of Dermatology, Faculty of Medicine, University of Tokyo, Tokyo, Japan.
The American Journal of Pathology
|March 25, 2004
Summary
Scleroderma fibroblasts show increased integrin alphavbeta5, enhancing vitronectin binding and inhibiting plasmin-mediated proteolysis, potentially contributing to fibrosis. This suggests alphavbeta5 as a therapeutic target for scleroderma.
Area of Science:
- Cell Biology
- Biochemistry
- Dermatology
Background:
- Integrin alphavbeta5 binds vitronectin, a protein in the extracellular matrix.
- Matrix-bound vitronectin can inhibit the plasmin-mediated proteolytic cascade by stabilizing plasminogen activator inhibitor-1.
Purpose of the Study:
- To compare alphavbeta5 and matrix-bound vitronectin levels in normal and scleroderma fibroblasts.
- To investigate the association between alphavbeta5, vitronectin, and fibrosis in scleroderma.
Main Methods:
- Immunohistochemistry to detect alphavbeta5 subunits and vitronectin.
- Comparing integrin and vitronectin levels between normal and scleroderma fibroblasts.
- Transient overexpression of alphavbeta5 in normal fibroblasts to assess its effect on collagen promoter activity and PAI-1 activation.
Main Results:
- Integrin alphavbeta5 was upregulated in scleroderma fibroblasts.
- Increased alphavbeta5 enhanced vitronectin binding and led to vitronectin-dependent activation of plasminogen activator inhibitor-1 (PAI-1).
- Overexpression of alphavbeta5 in normal fibroblasts enhanced collagen promoter activity and PAI-1 activity.
Conclusions:
- Upregulated alphavbeta5 in scleroderma fibroblasts may drive phenotypical alterations.
- The study suggests alphavbeta5 contributes to fibrosis by suppressing the pericellular proteolytic cascade.
- Integrin alphavbeta5 is implicated in the pathogenesis of scleroderma.