Increased gelatinase activity in systemic sclerosis dermal fibroblast cultures with unaltered gelatinase A mRNA expression.
Gelatinase A is one of the matrix metalloproteinases, the principle enzymes degrading extracellular matrix (ECM) and basement membrane components. The aim of this study was to study gelatinase expression in systemic sclerosis (SSc). Fibroblasts were grown from uninvolved and involved skin of SSc patients and from healthy controls. Gelatinase activity was assayed by degradation of tritium-labeled gelatin. Gelatinase A mRNA was quantitated by competitive reverse transcriptase-polymerase chain reaction (RT-PCR). Gelatinase activity was significantly increased in both uninvolved and involved SSc cultures. However, gelatinase A mRNA was unaltered in both cases. Neither SSc nor control skin fibroblasts expressed gelatinase B, indicating that the increased gelatinase activity is not due to gelatinase B induction. Gelatinase A is a specific basement membrane degrading enzyme, so increased gelatinase activity may be related to the pathophysiology of SSc by initiating microvascular damage and leakage of substances capable of producing further endothelial cell damage or fibroblast activation. Increased gelatinase activity in SSc fibroblasts seems to be regulated at translational and/or post-translational level.
Fakhoury
H
H
Department of Rheumatology, University of Manchester, Manchester, UK.
Hillarby
M C
MC
Weiss
J B
JB
D000328:Adult; D002478:Cells, Cultured; D020405:Dermis / Q000201:enzymology*; D005347:Fibroblasts / Q000201:enzymology; D018093:Gelatinases / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012595:Scleroderma, Systemic / Q000378:metabolism*
D012333:RNA, Messenger; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2