OBJECTIVE: In rheumatoid arthritis (RA) the synovial membrane proliferates and invades the underlying tissues. The cell-associated fibrinolytic system (urokinase-type plasminogen activator, uPA; uPA receptor, uPAR; plasminogen activator inhibitor-type 1, PAI-1) is pivotal in cell invasion and proliferation. For this reason, the expression and the role of such enzymatic system was investigated in synovial fibroblasts (SF) of normal and RA patients. METHODS: In SF obtained from RA patients and control subjects, uPA, uPAR and PAI-1 were measured by ELISA of cell lysates and culture medium and by RT-PCR of mRNAs. uPA was also studied by zymography. Proliferation was measured by cell counting and cell invasion with the Boyden chamber. RESULTS: RA-SF over-express uPAR and PAI-1 and are more prone than the normal counterpart to spontaneous and uPA-challenged invasion and proliferation, which are counteracted by antagonists of the fibrinolytic system. CONCLUSIONS: RA-SF display the fibrinolytic pattern and behaviour of invasive tumor-like cells. Antagonists of the fibrinolytic system are able to revert growth and invasion of both normal and RA-SF.
OBJECTIVE: In rheumatoid arthritis (RA) the synovial membrane proliferates and invades the underlying tissues. The cell-associated fibrinolytic system (urokinase-type plasminogen activator, uPA; uPA receptor, uPAR; plasminogen activator inhibitor-type 1, PAI-1) is pivotal in cell invasion and proliferation. For this reason, the expression and the role of such enzymatic system was investigated in synovial fibroblasts (SF) of normal and RApatients. METHODS: In SF obtained from RApatients and control subjects, uPA, uPAR and PAI-1 were measured by ELISA of cell lysates and culture medium and by RT-PCR of mRNAs. uPA was also studied by zymography. Proliferation was measured by cell counting and cell invasion with the Boyden chamber. RESULTS:RA-SF over-express uPAR and PAI-1 and are more prone than the normal counterpart to spontaneous and uPA-challenged invasion and proliferation, which are counteracted by antagonists of the fibrinolytic system. CONCLUSIONS:RA-SF display the fibrinolytic pattern and behaviour of invasive tumor-like cells. Antagonists of the fibrinolytic system are able to revert growth and invasion of both normal and RA-SF.
Authors: S Guiducci; A Del Rosso; M Cinelli; F Perfetto; R Livi; A Rossi; A Gabrielli; R Giacomelli; N Iori; G Fibbi; M Del Rosso; M Matucci Cerinic Journal: Arthritis Res Ther Date: 2005-09-08 Impact factor: 5.156
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Authors: V M Baart; R D Houvast; L F de Geus-Oei; P H A Quax; P J K Kuppen; A L Vahrmeijer; C F M Sier Journal: EJNMMI Res Date: 2020-07-28 Impact factor: 3.138
Authors: Laura Maggi; Francesca Margheri; Cristina Luciani; Manuela Capone; Maria Caterina Rossi; Anastasia Chillà; Veronica Santarlasci; Alessio Mazzoni; Rolando Cimaz; Francesco Liotta; Enrico Maggi; Lorenzo Cosmi; Mario Del Rosso; Francesco Annunziato Journal: PLoS One Date: 2016-04-28 Impact factor: 3.240