Shedding New Light on The Role of ανβ3 and α5β1 Integrins in Rheumatoid Arthritis

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.

The tellurium-based immunomodulator, AS101 ameliorates adjuvant-induced arthritis in rats

“…We believe that the anti‐arthritic and anti‐inflammatory driven response by AS101 depends, at least in part, upon its ability to interact with VLA‐4, thereby abrogating the infiltration of inflammatory/autoreactive VLA‐4 + immune cells into the joints. It is impossible to exclude the possible interference of AS101with other inflammatory/angiogenic integrins, such as αvβ3, α5β1, α1 and β2, which were previously demonstrated to play a significant role in the pathogenesis of RA [30,35]. However, evidence supports the relative specificity of AS101 for particular integrins, as demonstrated by the selective binding of AS101 to the thiol groups of vicinal cysteines on the α4‐chain in VLA‐4 (α4β1), but not α5β1 [16].…”

A Review on Chronic Pain in Rheumatoid Arthritis: A Focus on Activation of NR2B Subunit of N-Methyl-D-Aspartate Receptors

“…Furthermore, some RA patients may present with extraarticular symptoms at the eyes, mouth, lungs and heart. These symptoms may manifest in the form of keratitis, pulmonary granulomas (rheumatoid nodules), pericarditis/pleuritic and small-vessel vasculitis (3,4). The exact cause of RA remains unclear.…”

“…The binding of ανβ3-and α5β1-type integrins to their receptors can activate the SFKs. This activation takes place following the CAKβ activation that provides the SH2 docking sites on the C-terminal of NR2B subunit (4,21,33). The pro-inflammatory effect of integrin is also mediated via its activation of other signalling proteins, including RACK1 and MAPK following the Ras pathway.…”

“…The pro-inflammatory effect of integrin is also mediated via its activation of other signalling proteins, including RACK1 and MAPK following the Ras pathway. As a result, integrins leads to an increases production of nitric oxide (NO), prostaglandins E 2 (PGE 2 ) and vascular endothelial growth factor (VEGF) (4).…”

Anti-integrins

“…Pharmaceutics directed at integrins are under study in a wide variety of clinical states. These include inflammation (Arnaout 2016;Kourtzelis et al 2017)such as that of the intestinal tract (Catalan-Serra and Brenna 2018), in the vascular system (Huang and Frangogiannis 2018; Edwards and Bix 2019) and joints(Morshed et al 2019)cancer biology(Lavergne et al 2017;Raab-Westphal et al 2017;Leith et al 2018;Mousa et al 2018;Davis et al 2019) and angiogenesis(Mousa et al 2014;Davis et al 2015;Duro-Castano et al 2017;Guerrero and McCarty 2018).…”