Decreased integrin alpha 2, but normal response to TGF-beta in scleroderma fibroblasts.
The distribution and amount of integrin alpha2 were studied in cultured fibroblasts from normal subjects and scleroderma patients by immunofluorescence and immunoblotting using a monoclonal antibody against the human integrin alpha2 subunit. Integrin alpha2 was concentrated at the perinuclear regions in a dot-like pattern in normal fibroblasts on the glass coverslips until the 14th day after planting, and the staining pattern of integrin alpha2 was gradually changed to a dispersed dot-like pattern by the 19th day as examined by immunofluorescence microscopy by using the anti-integrin alpha2 antibody. No difference was observed in the distribution patterns between normal and scleroderma fibroblasts. By immunoblotting study, the amount of integrin alpha2 in scleroderma fibroblasts (n = 10) was less than that of normal fibroblasts (n = 10) (P < 0.01) in both cytosol and cytoskeleton-associated fractions. Furthermore, transforming growth factor beta (TGF-beta) increased the amount of integrin alpha2 in both normal fibroblasts and scleroderma cells by 33%. The total amount of integrin alpha2 in TGF-beta-stimulated scleroderma fibroblasts was less than that in TGF-beta-stimulated normal fibroblasts. These findings suggest that the amount of integrin alpha2, a collagen receptor, is reduced in scleroderma fibroblasts, but the integrin alpha2 production by TGF-beta stimulation is not impaired in scleroderma fibroblasts.
Osada
K
K
Department of Dermatology, Gifu University School of Medicine, Japan.
Seishima
M
M
Kitajima
Y
Y
Yaoita
H
H
Mori
S
S
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D002448:Cell Adhesion; D002478:Cells, Cultured; D018870:Endoplasmic Reticulum, Rough / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D039421:Integrin alpha2; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D012595:Scleroderma, Systemic / Q000378:metabolism* / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D015703:Antigens, CD; D039421:Integrin alpha2; D016212:Transforming Growth Factor beta