Abstract
ανβ3 and α5β1 are essential glycoproteins involved in the pathogenesis of rheumatoid arthritis (RA). Understanding of the role these integrins play in disease have been analyzed via description of cells-expressing ανβ3 and α5β1 and their mediators to trigger inflammation. ανβ3 and α5β1 facilitate cells-ECM and cell-cell communication, producing pro-inflammatory factors. Pro-inflammatory factors are essential for the building of undesirable new blood vessels termed angiogenesis which can further lead to destruction of bones and joints. Despite many attempts to target these glycoproteins, there are still some problems, therefore, there is still interest in understanding the synergistic role these integrins play in the pathogenesis of RA. The purpose of this review is to gain insights into the biological effects of ανβ3 and α5β1 in synovial tissues that are relevant to pathogenesis and therapy of RA.
Highlights
Rheumatoid arthritis (RA) is a chronic autoimmune disease with joints inflammation associated with synovitis, pannus formation and cartilage damage [1]
We have explained the role of αvβ3 and α5β1 integrins in RA. αvβ3 and α5β1 share similar binding ligand, structure, production sources and functional effects
These similarities assist αvβ3 and α5β1 to act as inflammatory and angiogenic factors in RA progression. αvβ3 and α5β1 are recognized as fibronectin receptors and in addition αvβ3 can bind to vitronectin, fibronegin, osteopontin and bone sialoprotein [6]
Summary
Rheumatoid arthritis (RA) is a chronic autoimmune disease with joints inflammation associated with synovitis, pannus formation and cartilage damage [1]. Upon pro-inflammatory mediators secretion such as matrix metalloproteinases (MMPs) and osteoclast inflammation, fibroblasts highly express αvβ or α5β1, is accompanied by increase proactivator, receptor activator of NF-κB ligand (RANKL) [18]. Ανβ3/lymphocytes or α5β1/lymphocytes adhesion to ECM ligands induces production of inflammatory factors that enhance survival and proliferation of synoviocytes and chondrocytes, Molecules 2019, 24, 1537 causing synovial tissue hyperplasia and destruction of bone and cartilage [17]. Macrophages and T helper (Th) cells-expressing αvβ and α5β1 produce IL-17, IL-1 and TNF-α cytokines These cytokines led to synovial fibroblasts activation to secrete pro-inflammatory cytokines such as MMPs, IL-6, tumor growth factor-β (TGF-β), RANKL and platelet-derived growth factor (PDGF) [1,7,34]. Αvβ and α5β1-stimulated cytokines bind to their receptors, causing MAPK and JAK/Stat pathway activation to regulate MMPs expression [42].
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