High plasminogen activator inhibitor type 2 expression is a hallmark of scleroderma fibroblasts in vitro.
Systemic scleroderma is a chronic disease, which leads to fibrosis of the skin and internal organs. Fibroblasts obtained from patients with this disease demonstrate an activated state in culture. We, in this study, report strong, constitutive overexpression of plasminogen activator inhibitor type-2 (PAI-2) in scleroderma fibroblasts and demonstrate that this induction observed at the mRNA and protein level is dependent on serum addition. Induced PAI-2 protein levels were restricted to the non-glycosylated 47-kDa form, which is located intracellularly. Induction was stable for at least 12 passages. No modulation by fibrogenic cytokines--for example, transforming growth factor-beta1 or connective tissue growth factor--or by antagonizing IL-1 receptors was observed. The data indicate that scleroderma fibroblasts are more sensitive to the induction of PAI-2 expression than control fibroblasts by a presently unknown factor in serum.
Kessler-Becker
Daniela
D
Department of Dermatology, University of Cologne, Cologne, Germany.
Smola
Sigrun
S
Krieg
Thomas
T
Eckes
Beate
B
D000328:Adult; D001706:Biopsy; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D017396:Plasminogen Activator Inhibitor 2 / Q000096:biosynthesis* / Q000378:metabolism; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000378:metabolism; D012594:Scleroderma, Localized / Q000378:metabolism*; D012595:Scleroderma, Systemic / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D017396:Plasminogen Activator Inhibitor 2; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D012313:RNA