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Review
. 2024 Apr 2;13(7):618.
doi: 10.3390/cells13070618.

The Role of Semaphorins in the Pathogenesis of Rheumatoid Arthritis

Jakub Rosik  1 , Joanna Kulpa  1 , Marcin Szczepanik  1 , Andrzej Pawlik  1
Affiliations
Review

The Role of Semaphorins in the Pathogenesis of Rheumatoid Arthritis

Jakub Rosik et al. Cells. .

Abstract

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Inflammation of the synovial fluid propagates the pathological process of angiogenesis. Semaphorins play a crucial role in the context of endothelial cell function, and their pleiotropic nature has various effects on the further development of RA. This narrative review summarises the various roles of semaphorins in the pathology of RA and whether they could play a role in developing novel RA treatment options.

Keywords: angiogenesis; rheumatoid arthritis; semaphorins.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Receptors to which Class 3 semaphorins bind are plexin A receptors and NRP-1 and NRP-2 co-receptors. Silencing the receptors modulates the response of FLS. SEMA4A binds to plexin B1, TIM 2, and D1 receptors. Silencing the receptors above leads to increased expression of IL-6 in RASFs. SEMA5A interacts with plexin A1 and plexin B3; this process induces SFs to release inflammatory compounds: IL-6, IL-8, and MMPs. By silencing the receptors, SF stimulation is blocked. The effect of SEMA7A is mediated through β1-integrin and plexin C1. These receptors are increased in patients with RA. By blocking them, the cytokine secretion is also blocked [21,22,23,24].
Figure 2
Figure 2
The role of semaphorins in the pathogenesis of RA (29–33). Interleukin 6 (IL-6), interleukin 8 (IL-8), tumor necrosis factor–alpha (TNF-α), vascular endothelial growth factor (VEGF), interferon-gamma (IFN-γ), neuropilin-1/2 (NRP-1/2), metalloproteinases (MMPs), interleukin 17 (IL-17), synovial fibroblasts (SFs).
Figure 3
Figure 3
SEMA3A importance as an immunoregulator [27].
Figure 4
Figure 4
The effects of class 3 semaphorins on rheumatoid arthritis fibroblast-like synoviocytes (RA FLSs) [22,49]. Abbreviations: foetal bovine serum (FBS); platelet-derived growth factor (PDGF).
Figure 5
Figure 5
The role of class 4 semaphorins in rheumatoid arthritis (RA) [23]. Abbreviations: C-reactive protein (CRP); Disease Activity Score 28 (DAS28); fibroblast-like synoviocytes (FLSs).
See this image and copyright information in PMC

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