Adhesion molecules in scleroderma: collagen binding integrins.
In summary, adhesion molecules are likely to play a prominent role in scleroderma pathogenesis and evolution. Endothelial adhesion molecules required for leukocyte extravasation are upregulated in affected tissue, though the mechanism is unclear. Certainly, endothelial adhesion molecule expression is seen in the context of other diseases not characterized by fibrosis. Adhesion molecules on the fibroblast, particularly those that play a role in fibroblast collagen interactions, may be very important. The ability of fibroblasts to organize collagen fibrils, and to exert forces across collagenous tissue, is likely to involve a prominent role of alpha 2 beta 1 integrin. Enhanced organization and contraction of newly formed collagen, as well as unregulated procollagen production, may be intimately linked in this disease process. At least two factors that strongly enhance fibroblast force generation could potentially influence other aspects of scleroderma. TGF beta is a potent stimulus for collagen production and has been found to be elevated in lesional scleroderma. Endothelin 1 is also a potent vasoconstrictor and is elevated in scleroderma patient serum as well [60,62-65]. Its apparent role in other fibrocontractive diseases suggests that its potential role in the pathogenesis of scleroderma deserves additional attention.
Kupper
T S
TS
Department of Dermatology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000502:physiology; D003094:Collagen / Q000032:analysis*; D005347:Fibroblasts / Q000737:chemistry; D006801:Humans; D019012:Integrin beta1; D016023:Integrins / Q000032:analysis* / Q000502:physiology; D007962:Leukocytes / Q000473:pathology; D012595:Scleroderma, Systemic / Q000473:pathology / Q000503:physiopathology*; D016212:Transforming Growth Factor beta / Q000502:physiology
D015815:Cell Adhesion Molecules; D019012:Integrin beta1; D016023:Integrins; D016212:Transforming Growth Factor beta; D003094:Collagen