Abstract：
:Rheumatoid arthritis (RA) is a systemic and chronic autoimmune inflammatory disorder affecting multiple joints. Various cytokines, chemokines and growth factors synergistically modulate the joint physiology leading to bone erosion and cartilage degradation. Other than these conventional mediators that are well established in the past, the newly identified plasminogen activator (PA) family of proteins have been witnessed to possess a multifactorial approach in mediating RA pathogenesis. One such family of proteins comprises of the urokinase-type plasminogen activator (uPA) and its receptor (uPAR)/soluble-type plasminogen activator receptor (suPAR). PA family of proteins are classified into two types namely: uPA and tissue type plasminogen activator (tPA). Both these subtypes have been implicated to play a key role in RA disease progression. However during RA pathogenesis, uPA secreted by neutrophils, chondrocytes, and monocytes are designated to interact with uPAR expressed on macrophages, fibroblast-like synoviocytes (FLS), chondrocytes and endothelial cells. Interaction of uPA/uPAR promotes the disease progression of RA through secretion of several cytokines, chemokines, growth factors and matrix metalloproteinases (MMPs). Moreover, uPA/uPAR initiates inflammatory responses in macrophages and FLS through activation of PI3K/Akt signaling pathways. Furthermore, uPAR plays a dual role in osteoclastogenesis under the presence/absence of growth factors like monocyte-colony stimulating factor (M-CSF). Overall, this review emphasizes the role of uPA/uPAR on various immune cells, signaling pathways and osteoclastogenesis involved in RA pathogenesis.
journal_name
Pharmacol Resjournal_title
Pharmacological researchauthors
Dinesh P,Rasool Mdoi
10.1016/j.phrs.2018.05.016subject
Has Abstractpub_date
2018-08-01 00:00:00pages
31-39eissn
1043-6618issn
1096-1186pii
S1043-6618(18)30597-8journal_volume
134pub_type
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journal_title：Pharmacological research
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journal_title：Pharmacological research
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pub_type： 杂志文章
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pub_type： 杂志文章
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更新日期：2018-08-01 00:00:00
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journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.2001.0853
更新日期：2001-09-01 00:00:00
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pub_type： 杂志文章
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更新日期：1991-01-01 00:00:00
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pub_type： 杂志文章,评审
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pub_type： 杂志文章
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更新日期：2004-08-01 00:00:00
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pub_type： 杂志文章
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更新日期：2005-02-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2018-07-01 00:00:00
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pub_type： 杂志文章
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更新日期：2005-03-01 00:00:00
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pub_type： 杂志文章,meta分析
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pub_type： 杂志文章,评审
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更新日期：2017-06-01 00:00:00
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pub_type： 杂志文章,评审
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更新日期：2010-03-01 00:00:00
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pub_type： 杂志文章
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更新日期：2003-02-01 00:00:00
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pub_type： 杂志文章
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更新日期：2009-10-01 00:00:00
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pub_type： 杂志文章
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更新日期：2020-12-19 00:00:00
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pub_type： 杂志文章
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更新日期：2021-01-01 00:00:00
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journal_title：Pharmacological research
pub_type： 杂志文章
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更新日期：2016-09-01 00:00:00
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journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1016/j.phrs.2016.03.041
更新日期：2016-06-01 00:00:00
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journal_title：Pharmacological research
pub_type： 杂志文章
doi：10.1006/phrs.1997.0212
更新日期：1997-07-01 00:00:00
