The Urokinase Plasminogen Activation System in Rheumatoid Arthritis: Pathophysiological Roles and Prospective Therapeutic Targets.
Rheumatoid arthritis
drug targets
plasminogen activation
uPA
uPAS
urokinase plasminogen activator.
Journal
Current drug targets
ISSN: 1873-5592
Titre abrégé: Curr Drug Targets
Pays: United Arab Emirates
ID NLM: 100960531
Informations de publication
Date de publication:
2019
2019
Historique:
received:
06
10
2018
revised:
12
11
2018
accepted:
28
11
2018
pubmed:
6
12
2018
medline:
6
8
2020
entrez:
6
12
2018
Statut:
ppublish
Résumé
Rheumatoid arthritis (RA) is a chronic and progressive inflammatory disease characterized in its early stages by synovial hyperplasia and inflammatory cell infiltration and later by irreversible joint tissue destruction. The plasminogen activation system (PAS) is associated with a wide range of physiological and pathophysiological states involving fibrinolysis, inflammation and tissue remodeling. Various components of the PAS are implicated in the pathophysiology of RA. Urokinase plasminogen activator (uPA) in particular is a pro-inflammatory mediator that appears to play an important role in the bone and cartilage destruction associated with RA. Clinical studies have shown that uPA and its receptor uPAR are overexpressed in synovia of patients with rheumatoid arthritis. Further, genetic knockdown and antibody-mediated neutralization of uPA have been shown to be protective against induction or progression of arthritis in animal models. The pro-arthritic role of uPA is differentiated from its haemodynamic counterpart, tissue plasminogen activator (tPA), which appears to play a protective role in RA animal models. This review summarises available evidence supporting the PAS as a critical determinant of RA pathogenesis and highlights opportunities for the development of novel uPAS-targeting therapeutics.
Identifiants
pubmed: 30516104
pii: CDT-EPUB-95020
doi: 10.2174/1389450120666181204164140
pmc: PMC6700755
doi:
Substances chimiques
Membrane Proteins
0
PLAU protein, human
0
Urokinase-Type Plasminogen Activator
EC 3.4.21.73
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
970-981Informations de copyright
Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.
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