Decreased Semaphorin3A expression correlates with disease activity and histological features of rheumatoid arthritis
Open Access
- 23 January 2013
- journal article
- research article
- Published by Springer Science and Business Media LLC in BMC Musculoskeletal Disorders
- Vol. 14 (1), 40
- https://doi.org/10.1186/1471-2474-14-40
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease of which the pathogenetic mechanisms are not fully understood. Semaphorin3A (Sema3A) has an immune regulatory role. Neuropilin1 (NRP1), the primary receptor for Sema3A, is also a receptor for vascular endothelial growth factor 165 (VEGF165). It has been shown that Sema3A competitively antagonizes VEGF165 signaling. This study investigated whether Sema3A is expressed in synovial tissues, and is associated with disease activity and the histological features of synovial tissues from RA patients. Human synovial tissues samples were obtained from RA and osteoarthritis (OA) patients. Disease activity of RA patients was calculated using the 28-joint Disease Activity Score based on C-reactive protein (DAS28-CRP). The histological features of RA synovial tissues were evaluated using Rooney’s inflammation scoring system. The localization of Sema3A, VEGF165 and NRP1 positive cells was immunohistochemically determined in synovial tissues. Expression levels of Sema3A, VEGF-A and NRP1 mRNA were determined using quantitative real-time polymerase chain reaction (qPCR). In OA specimens, Sema3A, VEGF165 and NRP1 proteins were expressed in the synovial lining and inflammatory cells beneath the lining. Immunohistochemistry revealed the protein expression of Sema3A in synovial lining cells was decreased in RA tissues compared with OA samples. qPCR analysis demonstrated a significant reduction of Sema3A mRNA levels in RA synovial tissue samples than in OA and a significant correlation of the ratio of Sema3A/VEGF-A mRNA expression levels with DAS28-CRP (R = −0.449, p = 0.013). Sema3A mRNA levels also correlated with Rooney’s inflammation score, especially in perivascular infiltrates of lymphocytes (R = −0.506, p = 0.004), focal aggregates of lymphocytes (R = −0.501, p = 0.005) and diffuse infiltrates of lymphocytes (R = −0.536, p = 0.002). Reduction of Sema3A expression in RA synovial tissues may contribute to pathogenesis of RA.Keywords
This publication has 57 references indexed in Scilit:
- Semaphorin 3A is a marker for disease activity and a potential immunoregulator in systemic lupus erythematosusArthritis Research & Therapy, 2012
- Semaphorins guide the entry of dendritic cells into the lymphatics by activating myosin IINature Immunology, 2010
- Neuropilin-1 in regulation of VEGF-induced activation of p38MAPK and endothelial cell organizationBlood, 2008
- Successful Inhibition of Tumor Development by Specific Class-3 Semaphorins Is Associated with Expression of Appropriate Semaphorin Receptors by Tumor CellsPLOS ONE, 2008
- Neuropilin-1 Expression on Regulatory T Cells Enhances Their Interactions with Dendritic Cells during Antigen RecognitionImmunity, 2008
- Semaphorin 3A suppresses VEGF-mediated angiogenesis yet acts as a vascular permeability factorBlood, 2008
- Cytokines in the pathogenesis of rheumatoid arthritisNature Reviews Immunology, 2007
- Comparison of Disease Activity Score (DAS)28- erythrocyte sedimentation rate and DAS28- C-reactive protein threshold valuesAnnals Of The Rheumatic Diseases, 2007
- The american rheumatism association 1987 revised criteria for the classification of rheumatoid arthritisArthritis & Rheumatism, 1988
- Development of criteria for the classification and reporting of osteoarthritis: Classification of osteoarthritis of the kneeArthritis & Rheumatism, 1986