Autocrine induction of gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF) and GLS-induced expression of matrix metalloproteinases in rheumatoid arthritis synoviocytes

H. Muro, Y. Waguri-Nagaya, Y. Mukofujiwara, T. Iwahashi, T. Otsuka, N. Matsui, A. Moriyama, K. Asai, T. Kato
1999 Rheumatology  
Objective. The purpose of this study was to examine how gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF ) is involved in the molecular mechanism of cartilage degradation in rheumatoid arthritis (RA) with special reference to the GLS-induced gene expression and protein synthesis of matrix metalloproteinase (MMP)-1 (collagenase-1) and MMP-3 (stromelysin-1). Methods. Fibroblast-like synoviocytes (FLSs) obtained from RA patients were cultured and stimulated by GLS. Changes
more » ... the expression levels of GLS, MMP-1 and MMP-3 were assessed by Northern blot analysis and reverse transcription-polymerase chain reaction (RT-PCR) for GLS, and by RT-PCR and enzyme-linked immunosorbent assay for MMPs and tissue inhibitor of metalloproteinase 1. Results. GLS demonstrated a self-induction of mRNA in cultured RA FLSs. GLS evoked a dose-dependent induction of MMP-1 and MMP-3 mRNAs, and subsequently their extracellular secretion. Conclusion. These findings suggest that GLS is a plausible pathogenic factor causing the extensive joint destruction in RA mediated via MMPs. K : Gliostatin, Platelet-derived endothelial cell growth factor, Thymidine phosphorylase, Rheumatoid arthritis, Matrix metalloproteinase.
doi:10.1093/rheumatology/38.12.1195 pmid:10587545 fatcat:asomibhdvzg4hnzpkqs6ziygrm